基于序列信息的核小体定位理论分析及预测
|
摘要
表观遗传学是后基因组时代的领舞者,核小体定位是表观遗传学的重要研究领域。核小体作为真核生物染色质高级结构的基本单位,不仅压缩了染色质结构,也发挥着重要的基因表达调控功能。核小体通过阻断蛋白因子与DNA序列的接触来完成对转录、复制、重组、修复、剪接、疾病的发生等过程的调控。研究真核生物的核小体定位不仅可以进一步阐明染色质高级结构的形成机制,也有助于揭示复杂的基因表达调控过程。
核小体在真核基因组的位置由DNA序列、染色质重塑子、转录机器、组蛋白修饰、组蛋白变体等因素共同决定。迄今为止,DNA序列仍是对核小体定位影响程度最大的单一因素。基于序列因素研究核小体定位的理论和实验工作已经不少。然而,现有的大多数核小体定位的理论工作的研究焦点集中于缠绕在组蛋白八聚体的核心DNA,对核小体核心颗粒之间的连接DNA关注较少。本文基于核小体定位的高通量测序数据,详细分析了核小体核心DNA和连接DNA的序列特征差异,并以DNA的序列特征为输入参数分别发展了位置相关得分函数(position-correlation scoring function, PCSF)和支持向量机(support vector machine, SVM)预测酵母等真核基因组的核小体定位。主要研究成果如下：
1.统计分析了酵母基因组核小体核心DNA(core DNA)和连接DNA(linker DNA)的K-mer(k=1,2,...6)特征和序列偏性特征Mk(i)(k=1,2,...6)。Core DNA内寡核苷酸片段的A+T含量低于linker DNA。A+T含量越高,序列的刚性越强,越不利于DNA的弯曲。因此,core DNA内由A和T组成的寡核苷酸片段含量低有助于核心DNA缠绕组蛋白八聚体。Linker DNA的k-mer偏性特征Mk(i)(k=1,2,...6)的值高于core DNA。因此,linker DNA的序列偏性强于core DNA,或者说linker DNA的序列保守性强于core DNA。这一发现为我们结合linker DNA的序列特征预测核小体定位提供了重要线索。
2.信息冗余参数Dk描述了DNA序列的词汇组成和语法结构。计算酵母、果蝇、线虫基因组的核小体定位序列的Dk值证实核小体core DNA和linker DNA的Dk值存在显著差异；core DNA和linker DNA序列都具有短程关联为主性特征。这种以短程关联为主的特性也解释了为什么大多数基于寡核苷酸片段或k-mer信息的核小体定位理论预测模型能够取得较好的预测效果。我们也证实,core DNA和linker DNA之间的信息含量差异性以及短程关联为主特征是普适的,既不受实验数据来源的牵制,也不受linker DNA长度的影响。
3.功率谱分析是识别DNA序列周期性信号的重要手段。酵母、果蝇、线虫基因组核小体core DNA和linker DNA的序列功率谱分析显示：三种模式生物的核小体core DNA序列内存在较明显的3-nt和10-nt周期性,且该周期信号强于相应的linker DNA序列。另外,我们也观察到了功率谱的物种特异性。
4.为进一步阐明碱基关联性对核小体定位的影响,分别计算了描述16种特定二核苷碱基关联的参数Fk在core DNA和linker DNA的分布。以核小体定位序列的参数Fk(k=0,1,2,...98)对应的1,584(99×16)维向量作为输入特征的支持向量机能够较好的区分H. sapiens, O. latipes, C. elegans, C. albicans和S. cerevisiae的core DNA和linker DNA,预测平均总精度TA为76.05%,相关系数MCC为0.4876。
5.基于linker DNA的四联体偏性M4(i)特征构建了预测酵母基因组核小体定位的PCSF算法。该算法可以较好的区分核小体core DNA和linker DNA,五折交叉检验的敏感性和特异性平均值分别达到94.42%和94.35%。我们也应用PCSF算法预测了酵母全基因组核小体占据率,预测的核小体占据率与Kaplan测定的体外核小体定位实验图谱的Pearson相关系数为0.761。预测的特定基因邻近区的核小体占据率也与实验结果较吻合。应用PCSF算法预测转录起始位点、转录终止位点、复制起始位点三类功能区域的核小体占据率图谱,能够识别出关键的核小体缺乏区。PCSF算法可以作为核小体定位理论预测的有效工具。
Epigenetics is an important frontier and a new research hotspot in the post-genomic era. Nucleosome positioning is a major area of epigenetics. As the basic building block of higher-order chromosome structure, nucleosome not only provides the measure of packing genomic DNA, but also is involved with gene expression and regulation. By controlling DNA accessibility, nucleosome regulates various biological processes, such as DNA transcription, DNA replication, DNA recombination, DNA repair, mRNA splicing, and disease development, etc. Investigation of the nucleosome positioning across eukaryotic genomes can contribute to elucidate the formation mechanism of higher-order chromosome structure and is helpful for uncovering intricate gene expression and regulation.
Nucleosome positioning along genome is determined by many factors including DNA sequence preferences, chromatin remodeling complex, transcriptional machinery, histone posttranslational modification, histone variant, etc. Intrinsic DNA sequence preferences of the nucleosome have been shown to be the most important factor over other factors recognized so far. Many theoretical and experimental studies of nucleosome positioning based on DNA sequence have existed. However, majority of theoretical studies paid more attention on core DNA wrapped around histone octamer and linker DNA between nucleosomes was given little attention. In this work, sequence characters of core DNA and linker DNA retrieved from high-resolution data of nucleosome positions were analyzed statistically. Based on DNA sequence signals, the novel position-correlation scoring function(PCSF) and support vector machine(SVM) were respectively developed to predict nucleosome positioning in eukaryotic genome.
Firstly, the distribution of K-mer(K=1,2,...6) and sequence bias parameter Mk(i)(k=1,2,...6) were analyzed systematically in core and linker sequences across S. cerevisiae. The oligonucleotides composed A and T are more enriched in linker DNA than core DNA. The higher A+T content, the stronger rigidity of sequence. Thus, the lower content of oligonucleotides comprised of A and T in core DNA are helpful for DNA wrapping. The bias of the k-mer frequency Mk(i)(K=1,2,...6) in linker regions is drastically higher than that in core regions. In other words, the bias of the k-mer frequency or sequence conservation in linker regions is stronger than in nucleosome core regions. This result provides an important clue to prediction of nucleosome occupancy combined sequence bias parameter.
Secondly, information redundancy Dk describes the vocabulary composition and grammar structure of genetic language. The calculated results of Dk across the genomes of S. cerevisiae, D. melanogaster, and C. elegans indicated that the value of Dk in core DNA is significantly different from that in linker DNA. The law of short-range correlation of the nucleotides is dominant in the nucleosome and linker DNA sequence was validated. This result probably decode the phenomenon that most of the theoretical models based on the frequencies of oligonucleotides or k-mer predicted nucleosome positioning with high accuracy. We also confirmed that the difference of information content between core DNA and linker DNA is universal. Neither the sequence length difference nor the difference of the method for constructing the dataset between the core DNA and linker DNA alters this difference.
Thirdly, power spectrum analysis is a popular method for detecting periodicity in DNA sequences. Power spectrum of core DNA and linkr DNA acrocss S. cerevisiae, D. melanogaster, and C. elegans genomes showed that the3-nt and10-nt periodicities are obvious in the nucleosome DNA regions and are stronger than that in linker DNA regions for three model organisms. Besides, the specific power spectrum of different species was shown.
Fourthly, to further clarify the effect of nucleotide correlation on nucleosome positioning, the parameter Fk(k=0...98) was calculated to examine particular base correlation corresponding to the16dinucleotides in core DNA and linker DNA. Using a1,584-element(99×16) vector as input vectors, the SVM was used to classify core and linker DNA regions in Homo sapiens, Oryzias latipes, C. elegans, Candida albicans, and S. cerevisiae. This model obtained a good performance with an average total accuracy of76.05%and an average MCC of0.4876in five organisms.
Finally, a novel PCSF algorithm based on the bias of4-mer frequency M4(ⅰ) in linker sequences was developed to distinguish nucleosome vs linker sequences. The5-fold cross-validation demonstrated that this algorithm achieved a good performance with mean sensitivity of94.42%and specificity of94.35%. Next, the algorithm was used to predict nucleosome occupancy throughout the S. cerevisiae genome and a higher pearson correlation coefficient of0.761with the in vitro experiment nucleosome positioning map of16chromosomes was obtained. Besides, the nucleosome profiles surrounding specific gene are notably similar with experimental maps of nucleosome organization in vitro and in vivo. By analyzing the profiles of nucleosome occupancy predicted by PCSF in the vicinity of TSS, TTS and ACS, the pronounced nucleosome depleted regions can be confirmed. The results suggested that intrinsic DNA sequence preferences in linker regions have a significant impact on the nucleosome occupancy and PCSF algorithm is an effective tool to predict nucleosome positioning.
核小体在真核基因组的位置由DNA序列、染色质重塑子、转录机器、组蛋白修饰、组蛋白变体等因素共同决定。迄今为止,DNA序列仍是对核小体定位影响程度最大的单一因素。基于序列因素研究核小体定位的理论和实验工作已经不少。然而,现有的大多数核小体定位的理论工作的研究焦点集中于缠绕在组蛋白八聚体的核心DNA,对核小体核心颗粒之间的连接DNA关注较少。本文基于核小体定位的高通量测序数据,详细分析了核小体核心DNA和连接DNA的序列特征差异,并以DNA的序列特征为输入参数分别发展了位置相关得分函数(position-correlation scoring function, PCSF)和支持向量机(support vector machine, SVM)预测酵母等真核基因组的核小体定位。主要研究成果如下：
1.统计分析了酵母基因组核小体核心DNA(core DNA)和连接DNA(linker DNA)的K-mer(k=1,2,...6)特征和序列偏性特征Mk(i)(k=1,2,...6)。Core DNA内寡核苷酸片段的A+T含量低于linker DNA。A+T含量越高,序列的刚性越强,越不利于DNA的弯曲。因此,core DNA内由A和T组成的寡核苷酸片段含量低有助于核心DNA缠绕组蛋白八聚体。Linker DNA的k-mer偏性特征Mk(i)(k=1,2,...6)的值高于core DNA。因此,linker DNA的序列偏性强于core DNA,或者说linker DNA的序列保守性强于core DNA。这一发现为我们结合linker DNA的序列特征预测核小体定位提供了重要线索。
2.信息冗余参数Dk描述了DNA序列的词汇组成和语法结构。计算酵母、果蝇、线虫基因组的核小体定位序列的Dk值证实核小体core DNA和linker DNA的Dk值存在显著差异；core DNA和linker DNA序列都具有短程关联为主性特征。这种以短程关联为主的特性也解释了为什么大多数基于寡核苷酸片段或k-mer信息的核小体定位理论预测模型能够取得较好的预测效果。我们也证实,core DNA和linker DNA之间的信息含量差异性以及短程关联为主特征是普适的,既不受实验数据来源的牵制,也不受linker DNA长度的影响。
3.功率谱分析是识别DNA序列周期性信号的重要手段。酵母、果蝇、线虫基因组核小体core DNA和linker DNA的序列功率谱分析显示：三种模式生物的核小体core DNA序列内存在较明显的3-nt和10-nt周期性,且该周期信号强于相应的linker DNA序列。另外,我们也观察到了功率谱的物种特异性。
4.为进一步阐明碱基关联性对核小体定位的影响,分别计算了描述16种特定二核苷碱基关联的参数Fk在core DNA和linker DNA的分布。以核小体定位序列的参数Fk(k=0,1,2,...98)对应的1,584(99×16)维向量作为输入特征的支持向量机能够较好的区分H. sapiens, O. latipes, C. elegans, C. albicans和S. cerevisiae的core DNA和linker DNA,预测平均总精度TA为76.05%,相关系数MCC为0.4876。
5.基于linker DNA的四联体偏性M4(i)特征构建了预测酵母基因组核小体定位的PCSF算法。该算法可以较好的区分核小体core DNA和linker DNA,五折交叉检验的敏感性和特异性平均值分别达到94.42%和94.35%。我们也应用PCSF算法预测了酵母全基因组核小体占据率,预测的核小体占据率与Kaplan测定的体外核小体定位实验图谱的Pearson相关系数为0.761。预测的特定基因邻近区的核小体占据率也与实验结果较吻合。应用PCSF算法预测转录起始位点、转录终止位点、复制起始位点三类功能区域的核小体占据率图谱,能够识别出关键的核小体缺乏区。PCSF算法可以作为核小体定位理论预测的有效工具。
Epigenetics is an important frontier and a new research hotspot in the post-genomic era. Nucleosome positioning is a major area of epigenetics. As the basic building block of higher-order chromosome structure, nucleosome not only provides the measure of packing genomic DNA, but also is involved with gene expression and regulation. By controlling DNA accessibility, nucleosome regulates various biological processes, such as DNA transcription, DNA replication, DNA recombination, DNA repair, mRNA splicing, and disease development, etc. Investigation of the nucleosome positioning across eukaryotic genomes can contribute to elucidate the formation mechanism of higher-order chromosome structure and is helpful for uncovering intricate gene expression and regulation.
Nucleosome positioning along genome is determined by many factors including DNA sequence preferences, chromatin remodeling complex, transcriptional machinery, histone posttranslational modification, histone variant, etc. Intrinsic DNA sequence preferences of the nucleosome have been shown to be the most important factor over other factors recognized so far. Many theoretical and experimental studies of nucleosome positioning based on DNA sequence have existed. However, majority of theoretical studies paid more attention on core DNA wrapped around histone octamer and linker DNA between nucleosomes was given little attention. In this work, sequence characters of core DNA and linker DNA retrieved from high-resolution data of nucleosome positions were analyzed statistically. Based on DNA sequence signals, the novel position-correlation scoring function(PCSF) and support vector machine(SVM) were respectively developed to predict nucleosome positioning in eukaryotic genome.
Firstly, the distribution of K-mer(K=1,2,...6) and sequence bias parameter Mk(i)(k=1,2,...6) were analyzed systematically in core and linker sequences across S. cerevisiae. The oligonucleotides composed A and T are more enriched in linker DNA than core DNA. The higher A+T content, the stronger rigidity of sequence. Thus, the lower content of oligonucleotides comprised of A and T in core DNA are helpful for DNA wrapping. The bias of the k-mer frequency Mk(i)(K=1,2,...6) in linker regions is drastically higher than that in core regions. In other words, the bias of the k-mer frequency or sequence conservation in linker regions is stronger than in nucleosome core regions. This result provides an important clue to prediction of nucleosome occupancy combined sequence bias parameter.
Secondly, information redundancy Dk describes the vocabulary composition and grammar structure of genetic language. The calculated results of Dk across the genomes of S. cerevisiae, D. melanogaster, and C. elegans indicated that the value of Dk in core DNA is significantly different from that in linker DNA. The law of short-range correlation of the nucleotides is dominant in the nucleosome and linker DNA sequence was validated. This result probably decode the phenomenon that most of the theoretical models based on the frequencies of oligonucleotides or k-mer predicted nucleosome positioning with high accuracy. We also confirmed that the difference of information content between core DNA and linker DNA is universal. Neither the sequence length difference nor the difference of the method for constructing the dataset between the core DNA and linker DNA alters this difference.
Thirdly, power spectrum analysis is a popular method for detecting periodicity in DNA sequences. Power spectrum of core DNA and linkr DNA acrocss S. cerevisiae, D. melanogaster, and C. elegans genomes showed that the3-nt and10-nt periodicities are obvious in the nucleosome DNA regions and are stronger than that in linker DNA regions for three model organisms. Besides, the specific power spectrum of different species was shown.
Fourthly, to further clarify the effect of nucleotide correlation on nucleosome positioning, the parameter Fk(k=0...98) was calculated to examine particular base correlation corresponding to the16dinucleotides in core DNA and linker DNA. Using a1,584-element(99×16) vector as input vectors, the SVM was used to classify core and linker DNA regions in Homo sapiens, Oryzias latipes, C. elegans, Candida albicans, and S. cerevisiae. This model obtained a good performance with an average total accuracy of76.05%and an average MCC of0.4876in five organisms.
Finally, a novel PCSF algorithm based on the bias of4-mer frequency M4(ⅰ) in linker sequences was developed to distinguish nucleosome vs linker sequences. The5-fold cross-validation demonstrated that this algorithm achieved a good performance with mean sensitivity of94.42%and specificity of94.35%. Next, the algorithm was used to predict nucleosome occupancy throughout the S. cerevisiae genome and a higher pearson correlation coefficient of0.761with the in vitro experiment nucleosome positioning map of16chromosomes was obtained. Besides, the nucleosome profiles surrounding specific gene are notably similar with experimental maps of nucleosome organization in vitro and in vivo. By analyzing the profiles of nucleosome occupancy predicted by PCSF in the vicinity of TSS, TTS and ACS, the pronounced nucleosome depleted regions can be confirmed. The results suggested that intrinsic DNA sequence preferences in linker regions have a significant impact on the nucleosome occupancy and PCSF algorithm is an effective tool to predict nucleosome positioning.
引文
[1]Kornberg RD. Structure of chromatin. Ann. Rev. Biochem.[J],1977,46:931-954.
[2]Jansen A, Verstrepen KJ. Nucleosome positioning in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rew.[J],2011,75(2):301-320.
[3]Kossel A. Ueber einen peptoartigen bestandheil des zellkerns. Z. Physiol. Chem.[J],1884,8: 511-515.
[4]Kornberg RD. Chromatin structure:a repeating unit of histones and DNA. Science[J],1974, 184:868-871.
[5]Richmond TJ, Finch JT, Rushton B, et al. Structure of the nucleosome core particle at 7A resolution. Nature[J],1984,311:532-537.
[6]Finch JT, Lutter LC, Rhodes D, et al. Structure of nucleosome core particles of chromatin. Nature[J],1977,269:29-36.
[7]Luger K, Mader AW, Richmond RK, et al. Crystal Structure of the nucleosome core particle at 2.8A resolution. Nature[J],1997,389:251-260.
[8]Richmond TJ, Davey CA. The structure of DNA in the nucleosome core. Nature[J],2003,423: 145-150.
[9]Athey BD, Smith MF, Rankert DA, et al. The diameters of frozen-hydrated chromatin fibers increase with DNA linker length:evidence in support of variable diameter models for chromatin. J. CellBiol.[J],1990,111:795-806.
[10]Arya G, Maitra A, Grigoryev SA. A structural perspective on the where, how, why, and what of nucleosome positioning. Journal of Biomolecular Structure & Dynamics[J],2010,27(6): 803-820.
[11]Struhl K, Segal E. Determinants of nucleosome positioning. Nature structural & molecular biology[J],2013,20(3):267-273.
[12]Levitsky VG, Katokhin A, Podkolodnaya OA, et al. NPRD:Nucleosome positioning region database. Nucleic Acids Research[J],2005,33:D67-D70.
[13]Usher SL. Nucleosome positioning in Arabidopsis[D]. University of Warwick,2009.
[14]Ioshikhes I, Bolshoy A, Derenshteyn K, et al. Nucleosome DNA sequence pattern revealed by multiple alignment of experimentally mapped sequences. Journal of Molecular Biology[J], 1996,262:129-139.
[15]Drew HR, Travers AA. DNA bending and its relation to nucleosome positioning. J. Mol. Biol.[J],1985,186:773-790.
[16]Satchwell SC, Travers AA. Asymmetry and polarity of nucleosomes in chicken erythrocyte chromatin. EMBO J.[J],1989,8:229-238.
[17]Iyer VR. Nucleosome positioning:bringing order to the eukaryotic genome. Trends Cell Biol.[J],2012,22(5):250-256.
[18]Yuan GC, Liu YJ, Dion MF, et al. Genome-scale identification of nucleosome positions in S. cerevisiae. Science[J],2005,309:626-630.
[19]Johnson SM, Tan FJ, McCullough HL, et al. Flexibility and constraint in the nucleosome core landscape of Caenorhabditis elegans chromatin. Genome Res.[J],2006,16:1505-1516.
[20]Lee W, Tillo D, Bray N, et al. A high-resolution atlas of nucleosome occupancy in yeast. Nat. Genet.[J],2007,39:1235-1244.
[21]Ozsolak F, Song JS, Liu XS et al. High-throughput mapping of the chromatin structure of human promoter. Nat. Biotechnol.[J],2007,25:244-248.
[22]Albert I, Mavrich TN, Tomsho LP, et al. Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature[J],2007,446:572-576.
[23]Mavrich TN, Ioshikhes IP, Venters BJ, et al. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res.[J],2008,18: 1073-1083.
[24]Mavrich TN, Jiang C, Ioshikhes IP, et al. Nucleosome organization in the Drosophila genome. Nature[J],2008,453:358-362.
[25]Kaplan N, Moore IK, Fondufe-Mittendorf Y, et al. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature[J],2009,458:362-366.
[26]Valouev A, Ichikawa J, Tonthat T, et al. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res.[J],2008,18: 1051-1063.
[27]Schones DE, Cui K, Cuddapah S, et al. Dynamic regulation of nucleosome positioning in the human genome. Cell[J],2008,132(5):887-898.
[28]Zhang Y, Moqtaderi Z, Rattner BP et al. Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat. Struct. Mol. Biol.[J],2009,16(8):847-852.
[29]Chodavarapu RK, Feng SH, Bernatavichute YV, et al. Relationship between nucleosome positioning and DNA methylation. Nature[J],2010,466:388-392.
[30]Li ZY, Schug J, Tuteja G, et al. The nucleosome map of the mammalian liver. Nature structural & molecular biology[J],2011,18(6):742-747.
[31]Brogaard K, Xi L, Wang JP, et al. A map of nucleosome positions in yeast at base-pair resolution. Nature[J],2012,486(7404):496-501.
[32]Nalabothula N, Xi LQ, Bhattacharyya S, et al. Archaeal nucleosome positioning in vivo and in vitro is directed by primary sequence motifs. BMC Genomics[J],2013,14:391.
[33]Tolstorukov MY, Kharhenko PV, Park PJ. Analysis of primary structure of chromatin with next-generation sequencing. Epigenomics[J],2010,2:187-197.
[34]Segal E, Fondufe-Mittendorf Y, Chen L, et al. A genomic code for nucleosome positioning. Nature[J],2006,442:772-778.
[35]Kato M, Onishi Y, Wada-Kiyama Y, et al. Biochemical screening of stable dinucleosomes using DNA fragments from a dinucleosome DNA library. J. Mol. Biol.[J],2005,350(2):215-227.
[36]Barski A, Cuddapah S, Cui K, et al. High-resolution profiling of histone methylations in the human genome. Cell[J],2007,129(4):823-837.
[37]Robertson AG, Bilenky M, Tam A, et al. Genome-wide relationship between histone H3 lysine 4 mono-and tri-methylation and transcription factor binding. Genome Res.[J],2008,18(12): 1906-1917.
[38]Wang Z, Zang C, Rosenfeld JA, et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet.[J],2008,40(7):897-903.
[39]Jin C, Zang C, Wei G, et al. H3.3/H2A.Z double variant-containing nucleosomes mark nucleosome-free regions of active promoters and other regulatory regions. Nat. Genet.[J],2009, 41(8):941-945.
[40]Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature[J],2007,448(7153):553-560.
[41]Nishida H, Motoyama T, Yamamoto S, et al. Genome-wide maps of mono-and di-nucleosomes of Aspergillus fumigatus. Bioinformatics[J],2009,25(18):2295-2297.
[42]Sasaki S, Mello CC, Shimada A, et al. Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites. Science[J],2009,323(5912):401-404.
[43]Westenberger SJ, Cui L, Dharia N, et al. Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes. BMC Genomics[J],2009,10:610.
[44]Chang GS, Noegel AA, Mavrich TN, et al. Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium. Genome Research[J],2012,22(6): 1098-1106.
[45]Nishida H, Kondo S, Matsumoto T, et al. Characteristics of nucleosomes and linker DNA regions on the genome of the basidiomycete Mixia osmundae revealed by mono-and dinucleosome mapping. Open Biology[J],2012,2(4):120043.
[46]Thastrom A, Lowary PT, Widlund HR, et al. Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences. J. Mol. Biol.[J],1999,288: 213-229.
[47]Boffelli D, De Santis P, Palleschi A, et al. The curvature vector in nucleosomal DNAs and theoretical prediction of nucleosome positioning. Biophys. Chem.[J],1991,39:127-136.
[48]Gabdank I, Barash D, Trifonov EN. FineStr:a web server for single-base-resolution nucleosome positioning. Bioinformatics[J],2010,26(6):845-846.
[49]Trifonov EN. Base pair stacking in nucleosome DNA and bendability sequence pattern. J. Theor. Biol.[J],2010,263:337-339.
[50]Rapoport AE, Frenkel ZM, Trifonov EN. Nucleosome positioning pattern derived from oligonucleotide compositions of genomic sequences. J. Biomol. Struct. Dyn.[J],2011,28: 567-574.
[51]Suter B, Schnappauf G, Thoma F. Poly(dA-dT) sequences exist as rigid DNA structures in nucleosome-free yeast promoters in vivo. Nucleic Acids Res.[J],2000,28:4083-4089.
[52]Segal E, Widom J. Poly(dA:dT) tracts:major determinants of nucleosome organization. Curr. Opin. Struct. Biol.[J],2009,19:65-71.
[53]Segal E, Widom J. What controls nucleosome positions? Trends Genet.[J],2009,25:335-343.
[54]Field Y, Kaplan N, Fondufe-Mittendorf Y, et al. Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLoS Comput. Biol.[J],2008,4:e100216.
[55]Nelson HCM, Finch JT, Luisi BF, et al. The structure of an oligo(dA).oligo(dT) tract and its biological implications. Nature[J],1987,330:221-226.
[56]McCall M, Brown T, Kennard O. The crystal structure of d(G-G-G-G-C-C-C-C). A model for poly(dG).poly(dC). J. Mol. Biol.[J],1985,183:385-396.
[57]Sekinger EA, Moqtaderi Z, Struhl K. Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast. Mol. Cell[J], 2005,18:735-748.
[58]Hughes A, Jin Y, Rando OJ, et al. A functional evolutionary approach to identify determinants of nucleosome positioning:a unifying model for establishing the genome-wide pattern. Mol. Cell[J],2012,48:5-15.
[59]Tirosh I, Barkai N. Two strategies for gene regulation by promoter nucleosomes. Genome Res.[J],2008,18:1084-1091.
[60]Hartley PD, Madhani HD. Mechanisms that specify promoter nucleosome location and identity. Cell[J],2009,137:445-458.
[61]Lantermann AB, Straub T, Stralfors A, et al. Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae. Nat. Struct. Mol. Biol.[J],2010,17:251-257.
[62]Tsankov A, Yanagisawa Y, Rhind N, et al. Evolutionary divergence of intrinsic and trans-regulated nucleosome positioning sequences reveals plastic rules for chromatin organization. Genome Res.[J],2011,21:1851-1862.
[63]Tsankov AM, Thompson DA, Socha A, et al. The role of nucleosome positioning in the evolution of gene regulation. PLoS Biol.[J],2010,8:e1000414.
[64]Zhang Z, Wippo CJ, Wal M, et al. A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science[J],2011,332:977-980.
[65]Gkikopoulos T, Schofield P, Singh V, et al. A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome organization. Science[J],2011,333:1758-1760.
[66]Weiner A, Hughes A, Yassour M, et al. High-resolution nucleosome mapping reveals transcription-dependent promoter packaging. Genome Res.[J],2010,20:90-100.
[67]Radman-Livaja M, Rando OJ. Nucleosome positioning:how is it established, and why does it matter? Dev. Biol.[J],2010,339:258-266.
[68]Zhang Y, Moqtaderi Z, Rattner BP, et al. Evidence against a genomic code for nucleosome positioning. Nat. Struct. Mol. Biol.[J],2010,17:920-923.
[69]Tillo D, Kaplan N, Moore IK, et al. High nucleosome occupancy is encoded at human regulatory sequences. PLoS One[J],2010,5:e9129.
[70]Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu. Rev. Biochem.[J],2009,78:273-304.
[71]Fyodorov DV, Kadonaga JT. Dynamics of ATP-dependent chromatin assembly by ACF. Nature[J],2002,418:897-900.
[72]Rippe K, Schrader A, Riede P, et al. DNA sequence-and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes. Proc. Natl. Acad. Sci. USA[J],2007,104: 15635-15640.
[73]van Vugt JJ, de Jager M, Murawska M, et al. Multiple aspects of ATP-dependent nucleosome translocation by RSC and Mi-2 are directed by the underlying DNA sequence. PLoS One[J], 2009,4:e6345.
[74]Whitehouse I, Tsukiyama T. Antagonistic forces that position nucleosomes in vivo. Nat. Struct. Mol. Biol.[J],2006,13:633-640.
[75]Whitehouse I, Rando OJ, Delrow J, et al. Chromatin remodelling at promoters suppresses antisense transcription. Nature[J],2007,450:1031-1035.
[76]Guenther MG, Levine SS, Boyer LA, R. et al. A chromatin landmark and transcription initiation at most promoters in human cells. Cell[J],2007,130:77-88.
[77]Zeitlinger J, Stark A, Kellis M, et al. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat. Genet.[J],2007,39:1512-1516.
[78]Churchman LS, Weissman JS. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature[J],2011,469:368-373.
[79]Gilchrist DA, Dos Santos G, Fargo DC, et al. Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation. Cell[J],2010,143: 540-551.
[80]Singh J, Padgett RA. Rates of in situ transcription and splicing in large human genes. Nat. Struct. Mol. Biol.[J],2009,16:1128-1133.
[81]Cheng B, Price DH. Properties of RNA polymerase II elongation complexes before and after the P-TEFb-mediated transition into productive elongation. J. Biol. Chem.[J],2007,282: 21901-21912.
[82]Izban MG, Luse DS. Factor-stimulated RNA polymerase II transcribes at physiological elongation rates on naked DNA but very poorly on chromatin templates. J. Biol. Chem.[J], 1992,267:13647-13655.
[83]Koerber RT, Rhee HS, Jiang C, Pugh BF. Interaction of transcriptional regulators with specific nucleosomes across the Saccharomyces genome. Mol. Cell[J],2009,35:889-902.
[84]Schwabish MA, Struhl K. Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II. Mol. Cell. Biol.[J],2004,24:10111-10117.
[85]Studitsky VM, Clark DJ, Felsenfeld G A histone octamer can step around a transcribing polymerase without leaving the template. Cell[J],1994,76:371-382.
[86]Studitsky VM, Kassavetis GA, Geiduschek EP, et al. Mechanism of transcription through the nucleosome by eukaryotic RNA polymerase. Science[J],1997,278:1960-1963.
[87]Wasylyk B, Chambon P. Studies on the mechanism of transcription of nucleosomal complexes. Eur. J. Biochem.[J],1980,103:219-226.
[88]Shivaswamy S, Bhinge A, Zhao Y, et al. Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biol.[J],2008,6:e65.
[89]Venters BJ, Pugh BF. A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome. Genome Res.[J],2009,19:360-371.
[90]Fan X, Moqtaderi Z, Jin Y, et al. Nucleosome depletion at yeast terminators is not intrinsic and can occur by a transcriptional mechanism linked to 3'-end formation. Proc. Natl. Acad. Sci. U. S.A.[J],2010,107:17945-17950.
[91]Goh WS, Orlov Y, Li J, et al. Blurring of highresolution data shows that the effect of intrinsic nucleosome occupancy on transcription factor binding is mostly regional, not local. PLoS Comput. Biol.[J],2010,6:e1000649.
[92]Yarragudi A, Miyake T, Li R, et al. Comparison of ABF1 and RAP1 in chromatin opening and transactivator potentiation in the budding yeast Saccharomyces cerevisiae. Mol. Cell. Biol.[J], 2004,24:9152-9164.
[93]Anderson JD, Widom J. Sequence and position-dependence of the equilibrium accessibility of nucleosomal DNAtarget sites. J. Mol. Biol.[J],2000,296:979-987.
[94]Anderson JD, Thastrom A, Widom J. Spontaneous access of proteins to buried nucleosomal DNA target sites occurs via a mechanism that is distinct from nucleosome translocation. Mol. Cell. Biol.[J],2002,22:7147-7157.
[95]Poirier MG, Bussiek M, Langowski J, et al. Spontaneous access to DNA target sites in folded chromatin fibers. J. Mol. Biol.[J],2008,379:772-786.
[96]Fyodorov DV, Kadonaga JT. Chromatin assembly in vitro with purified recombinant ACF and NAP-1. Methods Enzymol.[J],2003,371:499-515.
[97]Polach KJ, Widom J. Mechanism of protein access to specific DNA sequences in chromatin:a dynamic equilibrium model for gene regulation. J. Mol. Biol.[J],1995,254:130-149.
[98]Adams CC, Workman JL. Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative. Mol. Cell. Biol.[J],1995,15:1405-1421.
[99]Pal S, Cantor AB, Johnson KD, et al. Coregulator-dependent facilitation of chromatin occupancy by GATA-1. Proc. Natl. Acad. Sci. U. S. A.[J],2004,101:980-985.
[100]Garbett KA, Tripathi MK, Cencki B, et al. Yeast TFIID serves as a coactivator for Raplp by direct protein-protein interaction. Mol. Cell. Biol.[J],2007,27:297-311.
[101]Gartenberg MR. The Sir proteins of Saccharomyces cerevisiae: mediators of transcriptional silencing and much more. Curr. Opin. Microbiol.[J],2000,3:132-137.
[102]Kurtz S, Shore D. RAP1 protein activates and silences transcription of mating-type genes in yeast. Genes Dev.[J],1991,5:616-628.
[103]Shore D. RAP1:a protean regulator in yeast. Trends Genet.[J],1994,10:408-412.
[104]Yu L, Morse RH. Chromatin opening and transactivator potentiation by RAP1 in Saccharomyces cerevisiae. Mol. Cell. Biol.[J],1999,19:5279-5288.
[105]Anderson JD, Lowary PT, Widom J. Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites. J. Mol. Biol.[J],2001,307:977-985.
[106]Polach KJ, Lowary PT, Widom J. Effects of core histone tail domains on the equilibrium constants for dynamic DNA site accessibility in nucleosomes. J. Mol. Biol.[J],2000,298: 211-223.
[107]Widlund HR, Vitolo JM, Thiriet C, et al. DNA sequence-dependent contributions of core histone tails to nucleosome stability:differential effects of acetylation and proteolytic tail removal. Biochemistry[J],2000,39:3835-3841.
[108]Yang Z, Zheng C, Hayes JJ. The core histone tail domains contribute to sequence-dependent nucleosome positioning. J. Biol. Chem.[J],2007,282:7930-7938.
[109]Hamiche A, Kang JG, Dennis C, et al. Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF. Proc. Natl. Acad. Sci. U. S. A.[J], 2001,98:14316-14321.
[110]Dion MF, Altschuler SJ, Wu LF, et al. Genomic characterization reveals a simple histone H4 acetylation code. Proc. Natl. Acad. Sci. U. S. A.[J],2005,102:5501-5506.
[111]Hassan AH, Prochasson P, Neely KE, et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell[J],2002,111: 369-379.
[112]Wang X, Hayes JJ. Acetylation mimics within individual core histone tail domains indicate distinct roles in regulating the stability of higher-order chromatin structure. Mol. Cell. Biol.[J], 2008,28:227-236.
[113]Raisner RM, Hartley PD, Meneghini MD, et al. Histone variant H2A.Z marks the 5'ends of both active and inactive genes in euchromatin. Cell[J],2005,123:233-248.
[114]Zhang H, Roberts DN, Cairns BR. Genome-wide dynamics of Htzl, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell[J],2005,123: 219-231.
[115]Guillemette, B, Bataille AR, Gevry N, et al. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS Biol.[J],2005, 3:e384.
[116]Luijsterburg MS, White MF, van Driel R, et al. The major architects of chromatin: architectural proteins in bacteria, archaea and eukaryotes. Crit. Rev. Biochem. Mol. Biol.[J], 2008,43:393-418.
[117]Travers A, Muskhelishvili G. A common topology for bacterial and eukaryotic transcription initiation? EMBO Rep.[J],2007,8:147-151.
[118]Campos EI, Reinberg D. Histones:annotating chromatin. Annu. Rev. Genet.[J],2009,43: 559-599.
[119]Suganuma T, Workman JL. Signals and combinatorial functions of histone modifications. Annu. Rev. Biochem.[J],2011,80:473-499.
[120]Hodges C, Bintu L, Lubkowska L, et al. Nucleosomal fluctuations govern the transcription dynamics of RNA polymerase II. Science[J],2009,325:626-628.
[121]Wyrick JJ, Holstege FC, Jennings EG, et al. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature[J],1999,402:418-421.
[122]Celona B, Weiner A, Di Felice F, et al. Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS Biol.[J],2011,9:e1001086.
[123]Wang X, Bai L, Bryant GO, et al. Nucleosomes and the accessibility problem. Trends Genet.[J],2011,27:487-492.
[124]Zaret KS, Carroll JS. Pioneer transcription factors: establishing competence for gene expression. Genes Dev.[J],2011,25:2227-2241.
[125]Simpson RT. Nucleosome positioning can affect the function of a cis-acting DNA element in vivo. Nature[J],1990,343(25):387-389.
[126]Lipford JR, Bell SP. Nucleosomes positioned by ORC facilitates the initiation of DNA replication. Molecular Cell[J],2001,7:21-30.
[127]Eaton ML, Galani K, Kang S, et al. Conserved nucleosome positioning defines replication origins. Genes & Development J],2010,24:748-753.
[128]Costas C, De la Paz Sanchez M, Stroud H, et al. Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks. Nat. Struct. Mol. Biol.[J],2011,18(3):395-400.
[129]Beckmann JS, Trifonov EN. Splice junctions follow a 205-base ladder. Proc. Natl. Acad. Sci. U.S.A.[J],1991,88:2380-2383.
[130]Tilgner H, Nikolaou C, Althammer S, et al. Nucleosome positioning as a determinant of exon recognition. Nat. Struct. Mol. Biol.[J],2009,16:996-1001.
[131]Keren-Shaul H, Lev-Maor G, Ast G Pre-mRNA splicing is a determinant of nucleosome organization. Plos One[J],2013,8(1):e53506.
[132]Munoz MJ, Perez Santangelo MS, Paronetto MP, et al. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell[J],2009,137:708-720.
[133]Ioshikhes IP, Albert I, Zanton SJ, et al. Nucleosome positions predicted through comparative genomics. Nat. Genet.[J],2006,38:1210-1215.
[134]Peckham HE, Thurman RE, Fu YT, et al. Nucleosome positioning signals in genomic DNA. Genome Res.,2007,17:1170-1177.
[135]Yuan GC, Liu JS. Genomic sequence is highly predictive of local nucleosome depletion. PLoS Comput. Biol.[J],2008,4:e13.
[136]Tillo D, Hughes TR. G+C content dominates intrinsic nucleosome occupancy. BMC Bioinformatics[J],2009,10:442.
[137]Collings CK, Fernandez AG, Pitschka CG, et al. Oligonucleotide sequence motifs as nucleosome positioning signals. PLoS One[J],2010,5:e10933.
[138]Reynolds SM, Bilmes JA, Noble WS. Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens. PLoS Comput. Biol.[J],2010,6:e1000834.
[139]Gabdank I, Barash D, Trifonov EN. Nucleosome DNA bendability matrix (C. elegans). J. Biomol. Struct. Dyn.[J],2009,26:403-412.
[140]van der Heijden T, van Vugt JJ, Logie C, et al. Sequence-based prediction of single nucleosome positioning and genome-wide nucleosome occupancy. Proc. Natl. Acad. Sci. U.S.A.[J],2012,109(38):E2514-E2522.
[141]Zhao XJ, Pei ZY, Liu J, et al. Prediction of nucleosome DNA formation potential and nucleosome positioning using increment of diversity combined with quadratic discriminant analysis, Chromosome Res.[J],2010,18:777-785.
[142]Wang JY, Wang JY, Liu GQ. Calculation of nucleosomal DNA deformation energy:its implication for nucleosome positioning. Chromosome Res.[J],2012,20:889-902.
[143]Li QZ, Lin H. The recognition and prediction of sigma 70 promoter in Escherichia coli K-12. J. Theor. Biol.[J],2006,242(1):135-141.
[144]Zuo YC, Li QZ. Analysis of plant TATA and TATA-less promoters by using sequence and structure features. Progress in Bionchemistry and Biophysics[J],2009,36(7):863-871.
[145]Zuo YC, Li QZ. Identification of TATA and TATA-less promoters in plant genomes by integrating diversity measure, GC-Skew and DNA geometric flexibility. Genomics[J],2011, 97:112-120.
[146]Chen KF, Meng QS, Ma LN, et al. A novel DNA sequence periodicity decodes nucleosome positioning. Nucleic Acids Res.[J],2008,36:6228-6236.
[147]Chen KF, Wang L, Yang M, et al. Sequence signature of nucleosome positioning in Caenorhabditis elegans. Genomics Proteomics & Bioinformatics[J],2010,8:90-102.
[148]李春喜,姜丽娜,邵云等.生物统计学(M).第三版.北京：科学出版社,2005.
[149]杜荣骞.生物统计学(M).第二版.北京：高等教育出版社,2003.
[150]Mann HB, Whitney DR. On a test of whether one of two random variables is stochastically larger than the other. Annals of Mathematical Statistics[J],1947,18(1):50-60.
[151]林昊.基因启动子、蛋白质结构类及芋螺毒素超家族的理论预测[D].内蒙古大学,2007年.
[152]杨磊.转录因子结合位点和动物毒素的分析与预测[D].内蒙古大学,2010年.
[153]Cortes C, Vapnik V. Support Vector Networks. Machine learning[J],1995,20:273-297.
[154]Chen W, Lin H, Feng PM, et al. iNuc-PhysChem:a sequence-based predictor for identifying nucleosomes via physicochemical properties. PLoS One[J],2012,7(10):e47843.
[155]Fan GL, Li QZ. Predicting protein submitochondria locations by combining different descriptors into the general form of Chou's pseudo amino acid composition. Amino Acids[J], 2012,43(2):545-555.
[156]Sonnenburg S, Zien A, Ratsch G. ARTS:accurate recognition of transcription starts in human. Bioinformatics[J],2006,22(14):e472-e480.
[157]Liu GQ, Liu J, Cui XJ, et al. Sequence-dependent prediction of recombination hotspots in Saccharomyces cerevisiae. Journal of Theoretical Biology[J],2012,293:49-54.
[158]Chen W, Feng PM, Lin H, et al. iRSpot-PseDNC:identify recombination spots with pseudo dinucleotide composition. Nucleic Acids Res.[J],2013,41(6):e68.
[159]Li T, Li QZ, Liu S, et al. PreDNA:accurate prediction of DNA-binding sites in proteins by integrating sequence and geometric structure information. Bioinformatics[J],2013,29(6): 678-685.
[160]Hua S, Sun Z. A novel method of protein secondary structure prediction with high segment overlap measure:support vector machine approach. J. Mol. Biol.[J],2001,308(2):397-407.
[161]Noble WS. Support vector machine applications in computational biology [M]. In Kernel methods in computational biology. Edited by Schoelkopf B, Tsuda K, Vert JP. Cambridge (Massachusetts):MIT Press,2004.71-92.
[162]Chang CC, Lin CJ. LIBSVM:a library for support vector machines. ACM Trans Intell Syst Technol[J],2011,2:1-27.
[163]Xing YQ, Liu GQ, Zhao XJ, et al. An analysis and prediction of nucleosome positioning based on information content. Chromosome Research[J],2013,21:63-74.
[164]Xing YQ, Zhao XJ, Cai L. Prediction of nucleosome occupancy in Saccharomyces cerevisiae using position-correlation scoring function. Genomics[J],2011,98:359-366.
[165]Zhang LR, Luo LF. Splice site prediction with quadratic discriminant analysis using diversity measure. Nucleic Acids Research[J],2003,31(21):6214-6220.
[166]Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology[J],1982,143:29-36.
[167]Cui F, Zhurkin VB. Structure-based analysis of DNA sequence patterns guiding nucleosome positioning in vitro. J. Biomol. Struct. Dyn.[J],2010,27:821-841.
[168]Yanagi K, Prive GG, Dickerson RE. Analysis of local helix geometry in three B DNA decamers and eight dodecamers. J. Mol. Biol.[J],1991,217:201-214.
[169]Horz W, Altenburger W. Sequence specific cleavage of DNA by micrococcal nuclease. Nucleic Acids Res.[J],1981,9:2643-2658.
[170]Cui F, Zhnrkin VB. Distinctive sequence patterns in metazoan and yeast nucleosomes: implications for linker histone binding to AT-rich and methylated DNA. Nucleic Acids Res.[J], 2009,37:2818-2829.
[171]Cherry JM, Hong EL, Amundsen C, et al. Saccharomyces Genome Database:the genomics resource of budding yeast. Nucleic Acids Res.[J],2012,40:D700-D705
[172]McQuilton P, St Pierre SE, Thurmond J, the FlyBase Consortium. FlyBase 101-the basics of navigating Fly-Base. Nucleic Acids Res.[J],2012,40:D706-D714
[173]Dreszer TR, Karolchik D, Zweig AS, et al. The UCSC Genome Browser database:extensions and updates 2011. Nucleic Acids Res.[J],2012,40:D918-D923.
[174]Luo LF, Tsai L, Zhou YM. Informational parameters of nucleic acid and molecular evolution. J. Theor. Biol.[J],1988,130:351-361.
[175]Luo LF. Statistical correlation of nucleotides in a DNA sequence. Phys. Rev. E.[J],1998,58: 861-871.
[176]Grosse I, Buldyrev SY, Stanley HE. Average mutual information of coding and noncoding DNA. Pac. Symp. Biocomput.[J],2000,5:611-620.
[177]Grosse I, Herzel H, Buldyrev SV, et al. Species independence of mutual information in coding and noncoding DNA. Phys. Rev. E.[J],2000,61:5624-5629.
[178]Bauer M, Schuster SM, Sayood K. The average mutual information profile as a genomic signature. BMC Bioinformatics[J],2008,9:48.
[179]Su JZ, Zhang Y, Lv J, et al. CpG_MI:a novel approach for identifying functional CpG islands in mammalian genomes. Nucleic Acids Res.[J],2010,38:e6.
[180]Warnecke T, Batada NN, Hurst LD. The impact of the nucleosome code on protein-coding sequence evolution in yeast. PLoS Genet.[J],2008,4:e1000250.
[181]Swamy KBS, Chu WY, Wang CY, et al. Evidence of association between nucleosome occupancy and the evolution of transcription factor binding sites in yeast. BMC Evol. Biol.[J], 2011,11:150.
[182]Leach TJ, Mazzeo M, Chotkowski HL,et al. Histone H2A.Z is widely but nonrandomly distributed in chromosomes of Drosophila melanogaster. J. Biol. Chem.[J],2000,275: 23267-23272.
[183]Abbott DW, Ivanova VS, Wang X, et al. Characterization of the stability and folding of H2A.Z chromatin particles:implications for transcriptional activation. J. Biol. Chem.[J],2001,276: 41945-41949.
[184]Fukushima A, Ikemura T, Kinouchi M, et al. Periodicity in prokaryotic and eukaryotic genomes identified by power spectrum analysis. Gene[J],2002,300:203-211.
[185]Tanaka Y, Yamashita R, Suzuki Y, et al. Effects of Alu elements on global nucleosome positioning in the human genomes. BMC Genomics[J],2010,11:309.
[186]Radwan A, Younis A, Luykx P, et al. Prediction and analysis of nucleosome exclusion regions in the human genome. BMC Genomics[J],2008,9:186.
[187]Tanaka Y, Nakai K. An assessment of prediction algorithms for nucleosome positioning. Genome Inform.[J],2009,23:169-178.
[188]Zhang Z, Zhang YS, Chen W, et al. Prediction of nucleosome positioning using the dinucleotide absolute frequency of DNA fragment. Match-Commun. Math. Comput. Chem.[J], 2012,68:639-650.
[2]Jansen A, Verstrepen KJ. Nucleosome positioning in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rew.[J],2011,75(2):301-320.
[3]Kossel A. Ueber einen peptoartigen bestandheil des zellkerns. Z. Physiol. Chem.[J],1884,8: 511-515.
[4]Kornberg RD. Chromatin structure:a repeating unit of histones and DNA. Science[J],1974, 184:868-871.
[5]Richmond TJ, Finch JT, Rushton B, et al. Structure of the nucleosome core particle at 7A resolution. Nature[J],1984,311:532-537.
[6]Finch JT, Lutter LC, Rhodes D, et al. Structure of nucleosome core particles of chromatin. Nature[J],1977,269:29-36.
[7]Luger K, Mader AW, Richmond RK, et al. Crystal Structure of the nucleosome core particle at 2.8A resolution. Nature[J],1997,389:251-260.
[8]Richmond TJ, Davey CA. The structure of DNA in the nucleosome core. Nature[J],2003,423: 145-150.
[9]Athey BD, Smith MF, Rankert DA, et al. The diameters of frozen-hydrated chromatin fibers increase with DNA linker length:evidence in support of variable diameter models for chromatin. J. CellBiol.[J],1990,111:795-806.
[10]Arya G, Maitra A, Grigoryev SA. A structural perspective on the where, how, why, and what of nucleosome positioning. Journal of Biomolecular Structure & Dynamics[J],2010,27(6): 803-820.
[11]Struhl K, Segal E. Determinants of nucleosome positioning. Nature structural & molecular biology[J],2013,20(3):267-273.
[12]Levitsky VG, Katokhin A, Podkolodnaya OA, et al. NPRD:Nucleosome positioning region database. Nucleic Acids Research[J],2005,33:D67-D70.
[13]Usher SL. Nucleosome positioning in Arabidopsis[D]. University of Warwick,2009.
[14]Ioshikhes I, Bolshoy A, Derenshteyn K, et al. Nucleosome DNA sequence pattern revealed by multiple alignment of experimentally mapped sequences. Journal of Molecular Biology[J], 1996,262:129-139.
[15]Drew HR, Travers AA. DNA bending and its relation to nucleosome positioning. J. Mol. Biol.[J],1985,186:773-790.
[16]Satchwell SC, Travers AA. Asymmetry and polarity of nucleosomes in chicken erythrocyte chromatin. EMBO J.[J],1989,8:229-238.
[17]Iyer VR. Nucleosome positioning:bringing order to the eukaryotic genome. Trends Cell Biol.[J],2012,22(5):250-256.
[18]Yuan GC, Liu YJ, Dion MF, et al. Genome-scale identification of nucleosome positions in S. cerevisiae. Science[J],2005,309:626-630.
[19]Johnson SM, Tan FJ, McCullough HL, et al. Flexibility and constraint in the nucleosome core landscape of Caenorhabditis elegans chromatin. Genome Res.[J],2006,16:1505-1516.
[20]Lee W, Tillo D, Bray N, et al. A high-resolution atlas of nucleosome occupancy in yeast. Nat. Genet.[J],2007,39:1235-1244.
[21]Ozsolak F, Song JS, Liu XS et al. High-throughput mapping of the chromatin structure of human promoter. Nat. Biotechnol.[J],2007,25:244-248.
[22]Albert I, Mavrich TN, Tomsho LP, et al. Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature[J],2007,446:572-576.
[23]Mavrich TN, Ioshikhes IP, Venters BJ, et al. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res.[J],2008,18: 1073-1083.
[24]Mavrich TN, Jiang C, Ioshikhes IP, et al. Nucleosome organization in the Drosophila genome. Nature[J],2008,453:358-362.
[25]Kaplan N, Moore IK, Fondufe-Mittendorf Y, et al. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature[J],2009,458:362-366.
[26]Valouev A, Ichikawa J, Tonthat T, et al. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res.[J],2008,18: 1051-1063.
[27]Schones DE, Cui K, Cuddapah S, et al. Dynamic regulation of nucleosome positioning in the human genome. Cell[J],2008,132(5):887-898.
[28]Zhang Y, Moqtaderi Z, Rattner BP et al. Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat. Struct. Mol. Biol.[J],2009,16(8):847-852.
[29]Chodavarapu RK, Feng SH, Bernatavichute YV, et al. Relationship between nucleosome positioning and DNA methylation. Nature[J],2010,466:388-392.
[30]Li ZY, Schug J, Tuteja G, et al. The nucleosome map of the mammalian liver. Nature structural & molecular biology[J],2011,18(6):742-747.
[31]Brogaard K, Xi L, Wang JP, et al. A map of nucleosome positions in yeast at base-pair resolution. Nature[J],2012,486(7404):496-501.
[32]Nalabothula N, Xi LQ, Bhattacharyya S, et al. Archaeal nucleosome positioning in vivo and in vitro is directed by primary sequence motifs. BMC Genomics[J],2013,14:391.
[33]Tolstorukov MY, Kharhenko PV, Park PJ. Analysis of primary structure of chromatin with next-generation sequencing. Epigenomics[J],2010,2:187-197.
[34]Segal E, Fondufe-Mittendorf Y, Chen L, et al. A genomic code for nucleosome positioning. Nature[J],2006,442:772-778.
[35]Kato M, Onishi Y, Wada-Kiyama Y, et al. Biochemical screening of stable dinucleosomes using DNA fragments from a dinucleosome DNA library. J. Mol. Biol.[J],2005,350(2):215-227.
[36]Barski A, Cuddapah S, Cui K, et al. High-resolution profiling of histone methylations in the human genome. Cell[J],2007,129(4):823-837.
[37]Robertson AG, Bilenky M, Tam A, et al. Genome-wide relationship between histone H3 lysine 4 mono-and tri-methylation and transcription factor binding. Genome Res.[J],2008,18(12): 1906-1917.
[38]Wang Z, Zang C, Rosenfeld JA, et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet.[J],2008,40(7):897-903.
[39]Jin C, Zang C, Wei G, et al. H3.3/H2A.Z double variant-containing nucleosomes mark nucleosome-free regions of active promoters and other regulatory regions. Nat. Genet.[J],2009, 41(8):941-945.
[40]Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature[J],2007,448(7153):553-560.
[41]Nishida H, Motoyama T, Yamamoto S, et al. Genome-wide maps of mono-and di-nucleosomes of Aspergillus fumigatus. Bioinformatics[J],2009,25(18):2295-2297.
[42]Sasaki S, Mello CC, Shimada A, et al. Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites. Science[J],2009,323(5912):401-404.
[43]Westenberger SJ, Cui L, Dharia N, et al. Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes. BMC Genomics[J],2009,10:610.
[44]Chang GS, Noegel AA, Mavrich TN, et al. Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium. Genome Research[J],2012,22(6): 1098-1106.
[45]Nishida H, Kondo S, Matsumoto T, et al. Characteristics of nucleosomes and linker DNA regions on the genome of the basidiomycete Mixia osmundae revealed by mono-and dinucleosome mapping. Open Biology[J],2012,2(4):120043.
[46]Thastrom A, Lowary PT, Widlund HR, et al. Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences. J. Mol. Biol.[J],1999,288: 213-229.
[47]Boffelli D, De Santis P, Palleschi A, et al. The curvature vector in nucleosomal DNAs and theoretical prediction of nucleosome positioning. Biophys. Chem.[J],1991,39:127-136.
[48]Gabdank I, Barash D, Trifonov EN. FineStr:a web server for single-base-resolution nucleosome positioning. Bioinformatics[J],2010,26(6):845-846.
[49]Trifonov EN. Base pair stacking in nucleosome DNA and bendability sequence pattern. J. Theor. Biol.[J],2010,263:337-339.
[50]Rapoport AE, Frenkel ZM, Trifonov EN. Nucleosome positioning pattern derived from oligonucleotide compositions of genomic sequences. J. Biomol. Struct. Dyn.[J],2011,28: 567-574.
[51]Suter B, Schnappauf G, Thoma F. Poly(dA-dT) sequences exist as rigid DNA structures in nucleosome-free yeast promoters in vivo. Nucleic Acids Res.[J],2000,28:4083-4089.
[52]Segal E, Widom J. Poly(dA:dT) tracts:major determinants of nucleosome organization. Curr. Opin. Struct. Biol.[J],2009,19:65-71.
[53]Segal E, Widom J. What controls nucleosome positions? Trends Genet.[J],2009,25:335-343.
[54]Field Y, Kaplan N, Fondufe-Mittendorf Y, et al. Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLoS Comput. Biol.[J],2008,4:e100216.
[55]Nelson HCM, Finch JT, Luisi BF, et al. The structure of an oligo(dA).oligo(dT) tract and its biological implications. Nature[J],1987,330:221-226.
[56]McCall M, Brown T, Kennard O. The crystal structure of d(G-G-G-G-C-C-C-C). A model for poly(dG).poly(dC). J. Mol. Biol.[J],1985,183:385-396.
[57]Sekinger EA, Moqtaderi Z, Struhl K. Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast. Mol. Cell[J], 2005,18:735-748.
[58]Hughes A, Jin Y, Rando OJ, et al. A functional evolutionary approach to identify determinants of nucleosome positioning:a unifying model for establishing the genome-wide pattern. Mol. Cell[J],2012,48:5-15.
[59]Tirosh I, Barkai N. Two strategies for gene regulation by promoter nucleosomes. Genome Res.[J],2008,18:1084-1091.
[60]Hartley PD, Madhani HD. Mechanisms that specify promoter nucleosome location and identity. Cell[J],2009,137:445-458.
[61]Lantermann AB, Straub T, Stralfors A, et al. Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae. Nat. Struct. Mol. Biol.[J],2010,17:251-257.
[62]Tsankov A, Yanagisawa Y, Rhind N, et al. Evolutionary divergence of intrinsic and trans-regulated nucleosome positioning sequences reveals plastic rules for chromatin organization. Genome Res.[J],2011,21:1851-1862.
[63]Tsankov AM, Thompson DA, Socha A, et al. The role of nucleosome positioning in the evolution of gene regulation. PLoS Biol.[J],2010,8:e1000414.
[64]Zhang Z, Wippo CJ, Wal M, et al. A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science[J],2011,332:977-980.
[65]Gkikopoulos T, Schofield P, Singh V, et al. A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome organization. Science[J],2011,333:1758-1760.
[66]Weiner A, Hughes A, Yassour M, et al. High-resolution nucleosome mapping reveals transcription-dependent promoter packaging. Genome Res.[J],2010,20:90-100.
[67]Radman-Livaja M, Rando OJ. Nucleosome positioning:how is it established, and why does it matter? Dev. Biol.[J],2010,339:258-266.
[68]Zhang Y, Moqtaderi Z, Rattner BP, et al. Evidence against a genomic code for nucleosome positioning. Nat. Struct. Mol. Biol.[J],2010,17:920-923.
[69]Tillo D, Kaplan N, Moore IK, et al. High nucleosome occupancy is encoded at human regulatory sequences. PLoS One[J],2010,5:e9129.
[70]Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu. Rev. Biochem.[J],2009,78:273-304.
[71]Fyodorov DV, Kadonaga JT. Dynamics of ATP-dependent chromatin assembly by ACF. Nature[J],2002,418:897-900.
[72]Rippe K, Schrader A, Riede P, et al. DNA sequence-and conformation-directed positioning of nucleosomes by chromatin-remodeling complexes. Proc. Natl. Acad. Sci. USA[J],2007,104: 15635-15640.
[73]van Vugt JJ, de Jager M, Murawska M, et al. Multiple aspects of ATP-dependent nucleosome translocation by RSC and Mi-2 are directed by the underlying DNA sequence. PLoS One[J], 2009,4:e6345.
[74]Whitehouse I, Tsukiyama T. Antagonistic forces that position nucleosomes in vivo. Nat. Struct. Mol. Biol.[J],2006,13:633-640.
[75]Whitehouse I, Rando OJ, Delrow J, et al. Chromatin remodelling at promoters suppresses antisense transcription. Nature[J],2007,450:1031-1035.
[76]Guenther MG, Levine SS, Boyer LA, R. et al. A chromatin landmark and transcription initiation at most promoters in human cells. Cell[J],2007,130:77-88.
[77]Zeitlinger J, Stark A, Kellis M, et al. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat. Genet.[J],2007,39:1512-1516.
[78]Churchman LS, Weissman JS. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature[J],2011,469:368-373.
[79]Gilchrist DA, Dos Santos G, Fargo DC, et al. Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation. Cell[J],2010,143: 540-551.
[80]Singh J, Padgett RA. Rates of in situ transcription and splicing in large human genes. Nat. Struct. Mol. Biol.[J],2009,16:1128-1133.
[81]Cheng B, Price DH. Properties of RNA polymerase II elongation complexes before and after the P-TEFb-mediated transition into productive elongation. J. Biol. Chem.[J],2007,282: 21901-21912.
[82]Izban MG, Luse DS. Factor-stimulated RNA polymerase II transcribes at physiological elongation rates on naked DNA but very poorly on chromatin templates. J. Biol. Chem.[J], 1992,267:13647-13655.
[83]Koerber RT, Rhee HS, Jiang C, Pugh BF. Interaction of transcriptional regulators with specific nucleosomes across the Saccharomyces genome. Mol. Cell[J],2009,35:889-902.
[84]Schwabish MA, Struhl K. Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II. Mol. Cell. Biol.[J],2004,24:10111-10117.
[85]Studitsky VM, Clark DJ, Felsenfeld G A histone octamer can step around a transcribing polymerase without leaving the template. Cell[J],1994,76:371-382.
[86]Studitsky VM, Kassavetis GA, Geiduschek EP, et al. Mechanism of transcription through the nucleosome by eukaryotic RNA polymerase. Science[J],1997,278:1960-1963.
[87]Wasylyk B, Chambon P. Studies on the mechanism of transcription of nucleosomal complexes. Eur. J. Biochem.[J],1980,103:219-226.
[88]Shivaswamy S, Bhinge A, Zhao Y, et al. Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biol.[J],2008,6:e65.
[89]Venters BJ, Pugh BF. A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome. Genome Res.[J],2009,19:360-371.
[90]Fan X, Moqtaderi Z, Jin Y, et al. Nucleosome depletion at yeast terminators is not intrinsic and can occur by a transcriptional mechanism linked to 3'-end formation. Proc. Natl. Acad. Sci. U. S.A.[J],2010,107:17945-17950.
[91]Goh WS, Orlov Y, Li J, et al. Blurring of highresolution data shows that the effect of intrinsic nucleosome occupancy on transcription factor binding is mostly regional, not local. PLoS Comput. Biol.[J],2010,6:e1000649.
[92]Yarragudi A, Miyake T, Li R, et al. Comparison of ABF1 and RAP1 in chromatin opening and transactivator potentiation in the budding yeast Saccharomyces cerevisiae. Mol. Cell. Biol.[J], 2004,24:9152-9164.
[93]Anderson JD, Widom J. Sequence and position-dependence of the equilibrium accessibility of nucleosomal DNAtarget sites. J. Mol. Biol.[J],2000,296:979-987.
[94]Anderson JD, Thastrom A, Widom J. Spontaneous access of proteins to buried nucleosomal DNA target sites occurs via a mechanism that is distinct from nucleosome translocation. Mol. Cell. Biol.[J],2002,22:7147-7157.
[95]Poirier MG, Bussiek M, Langowski J, et al. Spontaneous access to DNA target sites in folded chromatin fibers. J. Mol. Biol.[J],2008,379:772-786.
[96]Fyodorov DV, Kadonaga JT. Chromatin assembly in vitro with purified recombinant ACF and NAP-1. Methods Enzymol.[J],2003,371:499-515.
[97]Polach KJ, Widom J. Mechanism of protein access to specific DNA sequences in chromatin:a dynamic equilibrium model for gene regulation. J. Mol. Biol.[J],1995,254:130-149.
[98]Adams CC, Workman JL. Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative. Mol. Cell. Biol.[J],1995,15:1405-1421.
[99]Pal S, Cantor AB, Johnson KD, et al. Coregulator-dependent facilitation of chromatin occupancy by GATA-1. Proc. Natl. Acad. Sci. U. S. A.[J],2004,101:980-985.
[100]Garbett KA, Tripathi MK, Cencki B, et al. Yeast TFIID serves as a coactivator for Raplp by direct protein-protein interaction. Mol. Cell. Biol.[J],2007,27:297-311.
[101]Gartenberg MR. The Sir proteins of Saccharomyces cerevisiae: mediators of transcriptional silencing and much more. Curr. Opin. Microbiol.[J],2000,3:132-137.
[102]Kurtz S, Shore D. RAP1 protein activates and silences transcription of mating-type genes in yeast. Genes Dev.[J],1991,5:616-628.
[103]Shore D. RAP1:a protean regulator in yeast. Trends Genet.[J],1994,10:408-412.
[104]Yu L, Morse RH. Chromatin opening and transactivator potentiation by RAP1 in Saccharomyces cerevisiae. Mol. Cell. Biol.[J],1999,19:5279-5288.
[105]Anderson JD, Lowary PT, Widom J. Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites. J. Mol. Biol.[J],2001,307:977-985.
[106]Polach KJ, Lowary PT, Widom J. Effects of core histone tail domains on the equilibrium constants for dynamic DNA site accessibility in nucleosomes. J. Mol. Biol.[J],2000,298: 211-223.
[107]Widlund HR, Vitolo JM, Thiriet C, et al. DNA sequence-dependent contributions of core histone tails to nucleosome stability:differential effects of acetylation and proteolytic tail removal. Biochemistry[J],2000,39:3835-3841.
[108]Yang Z, Zheng C, Hayes JJ. The core histone tail domains contribute to sequence-dependent nucleosome positioning. J. Biol. Chem.[J],2007,282:7930-7938.
[109]Hamiche A, Kang JG, Dennis C, et al. Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF. Proc. Natl. Acad. Sci. U. S. A.[J], 2001,98:14316-14321.
[110]Dion MF, Altschuler SJ, Wu LF, et al. Genomic characterization reveals a simple histone H4 acetylation code. Proc. Natl. Acad. Sci. U. S. A.[J],2005,102:5501-5506.
[111]Hassan AH, Prochasson P, Neely KE, et al. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell[J],2002,111: 369-379.
[112]Wang X, Hayes JJ. Acetylation mimics within individual core histone tail domains indicate distinct roles in regulating the stability of higher-order chromatin structure. Mol. Cell. Biol.[J], 2008,28:227-236.
[113]Raisner RM, Hartley PD, Meneghini MD, et al. Histone variant H2A.Z marks the 5'ends of both active and inactive genes in euchromatin. Cell[J],2005,123:233-248.
[114]Zhang H, Roberts DN, Cairns BR. Genome-wide dynamics of Htzl, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell[J],2005,123: 219-231.
[115]Guillemette, B, Bataille AR, Gevry N, et al. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS Biol.[J],2005, 3:e384.
[116]Luijsterburg MS, White MF, van Driel R, et al. The major architects of chromatin: architectural proteins in bacteria, archaea and eukaryotes. Crit. Rev. Biochem. Mol. Biol.[J], 2008,43:393-418.
[117]Travers A, Muskhelishvili G. A common topology for bacterial and eukaryotic transcription initiation? EMBO Rep.[J],2007,8:147-151.
[118]Campos EI, Reinberg D. Histones:annotating chromatin. Annu. Rev. Genet.[J],2009,43: 559-599.
[119]Suganuma T, Workman JL. Signals and combinatorial functions of histone modifications. Annu. Rev. Biochem.[J],2011,80:473-499.
[120]Hodges C, Bintu L, Lubkowska L, et al. Nucleosomal fluctuations govern the transcription dynamics of RNA polymerase II. Science[J],2009,325:626-628.
[121]Wyrick JJ, Holstege FC, Jennings EG, et al. Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature[J],1999,402:418-421.
[122]Celona B, Weiner A, Di Felice F, et al. Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS Biol.[J],2011,9:e1001086.
[123]Wang X, Bai L, Bryant GO, et al. Nucleosomes and the accessibility problem. Trends Genet.[J],2011,27:487-492.
[124]Zaret KS, Carroll JS. Pioneer transcription factors: establishing competence for gene expression. Genes Dev.[J],2011,25:2227-2241.
[125]Simpson RT. Nucleosome positioning can affect the function of a cis-acting DNA element in vivo. Nature[J],1990,343(25):387-389.
[126]Lipford JR, Bell SP. Nucleosomes positioned by ORC facilitates the initiation of DNA replication. Molecular Cell[J],2001,7:21-30.
[127]Eaton ML, Galani K, Kang S, et al. Conserved nucleosome positioning defines replication origins. Genes & Development J],2010,24:748-753.
[128]Costas C, De la Paz Sanchez M, Stroud H, et al. Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks. Nat. Struct. Mol. Biol.[J],2011,18(3):395-400.
[129]Beckmann JS, Trifonov EN. Splice junctions follow a 205-base ladder. Proc. Natl. Acad. Sci. U.S.A.[J],1991,88:2380-2383.
[130]Tilgner H, Nikolaou C, Althammer S, et al. Nucleosome positioning as a determinant of exon recognition. Nat. Struct. Mol. Biol.[J],2009,16:996-1001.
[131]Keren-Shaul H, Lev-Maor G, Ast G Pre-mRNA splicing is a determinant of nucleosome organization. Plos One[J],2013,8(1):e53506.
[132]Munoz MJ, Perez Santangelo MS, Paronetto MP, et al. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell[J],2009,137:708-720.
[133]Ioshikhes IP, Albert I, Zanton SJ, et al. Nucleosome positions predicted through comparative genomics. Nat. Genet.[J],2006,38:1210-1215.
[134]Peckham HE, Thurman RE, Fu YT, et al. Nucleosome positioning signals in genomic DNA. Genome Res.,2007,17:1170-1177.
[135]Yuan GC, Liu JS. Genomic sequence is highly predictive of local nucleosome depletion. PLoS Comput. Biol.[J],2008,4:e13.
[136]Tillo D, Hughes TR. G+C content dominates intrinsic nucleosome occupancy. BMC Bioinformatics[J],2009,10:442.
[137]Collings CK, Fernandez AG, Pitschka CG, et al. Oligonucleotide sequence motifs as nucleosome positioning signals. PLoS One[J],2010,5:e10933.
[138]Reynolds SM, Bilmes JA, Noble WS. Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens. PLoS Comput. Biol.[J],2010,6:e1000834.
[139]Gabdank I, Barash D, Trifonov EN. Nucleosome DNA bendability matrix (C. elegans). J. Biomol. Struct. Dyn.[J],2009,26:403-412.
[140]van der Heijden T, van Vugt JJ, Logie C, et al. Sequence-based prediction of single nucleosome positioning and genome-wide nucleosome occupancy. Proc. Natl. Acad. Sci. U.S.A.[J],2012,109(38):E2514-E2522.
[141]Zhao XJ, Pei ZY, Liu J, et al. Prediction of nucleosome DNA formation potential and nucleosome positioning using increment of diversity combined with quadratic discriminant analysis, Chromosome Res.[J],2010,18:777-785.
[142]Wang JY, Wang JY, Liu GQ. Calculation of nucleosomal DNA deformation energy:its implication for nucleosome positioning. Chromosome Res.[J],2012,20:889-902.
[143]Li QZ, Lin H. The recognition and prediction of sigma 70 promoter in Escherichia coli K-12. J. Theor. Biol.[J],2006,242(1):135-141.
[144]Zuo YC, Li QZ. Analysis of plant TATA and TATA-less promoters by using sequence and structure features. Progress in Bionchemistry and Biophysics[J],2009,36(7):863-871.
[145]Zuo YC, Li QZ. Identification of TATA and TATA-less promoters in plant genomes by integrating diversity measure, GC-Skew and DNA geometric flexibility. Genomics[J],2011, 97:112-120.
[146]Chen KF, Meng QS, Ma LN, et al. A novel DNA sequence periodicity decodes nucleosome positioning. Nucleic Acids Res.[J],2008,36:6228-6236.
[147]Chen KF, Wang L, Yang M, et al. Sequence signature of nucleosome positioning in Caenorhabditis elegans. Genomics Proteomics & Bioinformatics[J],2010,8:90-102.
[148]李春喜,姜丽娜,邵云等.生物统计学(M).第三版.北京：科学出版社,2005.
[149]杜荣骞.生物统计学(M).第二版.北京：高等教育出版社,2003.
[150]Mann HB, Whitney DR. On a test of whether one of two random variables is stochastically larger than the other. Annals of Mathematical Statistics[J],1947,18(1):50-60.
[151]林昊.基因启动子、蛋白质结构类及芋螺毒素超家族的理论预测[D].内蒙古大学,2007年.
[152]杨磊.转录因子结合位点和动物毒素的分析与预测[D].内蒙古大学,2010年.
[153]Cortes C, Vapnik V. Support Vector Networks. Machine learning[J],1995,20:273-297.
[154]Chen W, Lin H, Feng PM, et al. iNuc-PhysChem:a sequence-based predictor for identifying nucleosomes via physicochemical properties. PLoS One[J],2012,7(10):e47843.
[155]Fan GL, Li QZ. Predicting protein submitochondria locations by combining different descriptors into the general form of Chou's pseudo amino acid composition. Amino Acids[J], 2012,43(2):545-555.
[156]Sonnenburg S, Zien A, Ratsch G. ARTS:accurate recognition of transcription starts in human. Bioinformatics[J],2006,22(14):e472-e480.
[157]Liu GQ, Liu J, Cui XJ, et al. Sequence-dependent prediction of recombination hotspots in Saccharomyces cerevisiae. Journal of Theoretical Biology[J],2012,293:49-54.
[158]Chen W, Feng PM, Lin H, et al. iRSpot-PseDNC:identify recombination spots with pseudo dinucleotide composition. Nucleic Acids Res.[J],2013,41(6):e68.
[159]Li T, Li QZ, Liu S, et al. PreDNA:accurate prediction of DNA-binding sites in proteins by integrating sequence and geometric structure information. Bioinformatics[J],2013,29(6): 678-685.
[160]Hua S, Sun Z. A novel method of protein secondary structure prediction with high segment overlap measure:support vector machine approach. J. Mol. Biol.[J],2001,308(2):397-407.
[161]Noble WS. Support vector machine applications in computational biology [M]. In Kernel methods in computational biology. Edited by Schoelkopf B, Tsuda K, Vert JP. Cambridge (Massachusetts):MIT Press,2004.71-92.
[162]Chang CC, Lin CJ. LIBSVM:a library for support vector machines. ACM Trans Intell Syst Technol[J],2011,2:1-27.
[163]Xing YQ, Liu GQ, Zhao XJ, et al. An analysis and prediction of nucleosome positioning based on information content. Chromosome Research[J],2013,21:63-74.
[164]Xing YQ, Zhao XJ, Cai L. Prediction of nucleosome occupancy in Saccharomyces cerevisiae using position-correlation scoring function. Genomics[J],2011,98:359-366.
[165]Zhang LR, Luo LF. Splice site prediction with quadratic discriminant analysis using diversity measure. Nucleic Acids Research[J],2003,31(21):6214-6220.
[166]Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology[J],1982,143:29-36.
[167]Cui F, Zhurkin VB. Structure-based analysis of DNA sequence patterns guiding nucleosome positioning in vitro. J. Biomol. Struct. Dyn.[J],2010,27:821-841.
[168]Yanagi K, Prive GG, Dickerson RE. Analysis of local helix geometry in three B DNA decamers and eight dodecamers. J. Mol. Biol.[J],1991,217:201-214.
[169]Horz W, Altenburger W. Sequence specific cleavage of DNA by micrococcal nuclease. Nucleic Acids Res.[J],1981,9:2643-2658.
[170]Cui F, Zhnrkin VB. Distinctive sequence patterns in metazoan and yeast nucleosomes: implications for linker histone binding to AT-rich and methylated DNA. Nucleic Acids Res.[J], 2009,37:2818-2829.
[171]Cherry JM, Hong EL, Amundsen C, et al. Saccharomyces Genome Database:the genomics resource of budding yeast. Nucleic Acids Res.[J],2012,40:D700-D705
[172]McQuilton P, St Pierre SE, Thurmond J, the FlyBase Consortium. FlyBase 101-the basics of navigating Fly-Base. Nucleic Acids Res.[J],2012,40:D706-D714
[173]Dreszer TR, Karolchik D, Zweig AS, et al. The UCSC Genome Browser database:extensions and updates 2011. Nucleic Acids Res.[J],2012,40:D918-D923.
[174]Luo LF, Tsai L, Zhou YM. Informational parameters of nucleic acid and molecular evolution. J. Theor. Biol.[J],1988,130:351-361.
[175]Luo LF. Statistical correlation of nucleotides in a DNA sequence. Phys. Rev. E.[J],1998,58: 861-871.
[176]Grosse I, Buldyrev SY, Stanley HE. Average mutual information of coding and noncoding DNA. Pac. Symp. Biocomput.[J],2000,5:611-620.
[177]Grosse I, Herzel H, Buldyrev SV, et al. Species independence of mutual information in coding and noncoding DNA. Phys. Rev. E.[J],2000,61:5624-5629.
[178]Bauer M, Schuster SM, Sayood K. The average mutual information profile as a genomic signature. BMC Bioinformatics[J],2008,9:48.
[179]Su JZ, Zhang Y, Lv J, et al. CpG_MI:a novel approach for identifying functional CpG islands in mammalian genomes. Nucleic Acids Res.[J],2010,38:e6.
[180]Warnecke T, Batada NN, Hurst LD. The impact of the nucleosome code on protein-coding sequence evolution in yeast. PLoS Genet.[J],2008,4:e1000250.
[181]Swamy KBS, Chu WY, Wang CY, et al. Evidence of association between nucleosome occupancy and the evolution of transcription factor binding sites in yeast. BMC Evol. Biol.[J], 2011,11:150.
[182]Leach TJ, Mazzeo M, Chotkowski HL,et al. Histone H2A.Z is widely but nonrandomly distributed in chromosomes of Drosophila melanogaster. J. Biol. Chem.[J],2000,275: 23267-23272.
[183]Abbott DW, Ivanova VS, Wang X, et al. Characterization of the stability and folding of H2A.Z chromatin particles:implications for transcriptional activation. J. Biol. Chem.[J],2001,276: 41945-41949.
[184]Fukushima A, Ikemura T, Kinouchi M, et al. Periodicity in prokaryotic and eukaryotic genomes identified by power spectrum analysis. Gene[J],2002,300:203-211.
[185]Tanaka Y, Yamashita R, Suzuki Y, et al. Effects of Alu elements on global nucleosome positioning in the human genomes. BMC Genomics[J],2010,11:309.
[186]Radwan A, Younis A, Luykx P, et al. Prediction and analysis of nucleosome exclusion regions in the human genome. BMC Genomics[J],2008,9:186.
[187]Tanaka Y, Nakai K. An assessment of prediction algorithms for nucleosome positioning. Genome Inform.[J],2009,23:169-178.
[188]Zhang Z, Zhang YS, Chen W, et al. Prediction of nucleosome positioning using the dinucleotide absolute frequency of DNA fragment. Match-Commun. Math. Comput. Chem.[J], 2012,68:639-650.