Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein
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- 作者：Jing-Jing Zhang (1) (2)
Yi Zhu (1) (2)
Xiong-Fei Zhang (3)
Wen-Biao Liang (4)
Kun-Ling Xie (5)
Jin-Qiu Tao (5)
Yun-Peng Peng (5)
Ze-Kuan Xu (1) (2)
Yi Miao (1) (2) - 关键词：MUC4 ; Gene expression ; Down ; regulation ; Transcription factors ; Yin yang 1
- 刊名：Molecular Biology Reports
- 出版年：2013
- 出版时间：August 2013
- 年：2013
- 卷：40
- 期：8
- 页码：4913-4920
- 全文大小：369KB
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Yi Zhu (1) (2)
Xiong-Fei Zhang (3)
Wen-Biao Liang (4)
Kun-Ling Xie (5)
Jin-Qiu Tao (5)
Yun-Peng Peng (5)
Ze-Kuan Xu (1) (2)
Yi Miao (1) (2)
1. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China
2. Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China
3. Department of Biochemistry, Wenzhou Medical College, Wenzhou, 325035, People’s Republic of China
4. Transfusion Laboratory, Jiangsu Province Blood Center, Nanjing, 210029, People’s Republic of China
5. The First School of Clinical Medicine, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People’s Republic of China
文摘
The human mucin 4 (MUC4) is aberrantly expressed in pancreatic adenocarcinoma and tumor cell lines, while remaining undetectable in normal pancreas, indicating its important role in pancreatic cancer development. Although its transcriptional regulation has been investigated in considerable detail, some important elements remain unknown. The aim of the present study was to demonstrate the existence of a novel inhibitory element in the MUC4 promoter and characterize some of its binding proteins. By luciferase reporter assay, we located the inhibitory element between nucleotides ?530 and ?521 in the MUC4 promoter using a series of deletion and mutant reporter constructs. Electrophoretic mobility shift assay (EMSA) with Bxpc-3 cell nuclear extracts revealed that one protein or protein complex bind to this element. The proteins binding to this element were purified and identified as Yin Yang 1 (YY1) by mass spectrometry. Supershift assay and chromatin immunoprecipitation (ChIP) assay confirmed that YY1 binds to this element in vitro and in vivo. Moreover, transient YY1 overexpression significantly inhibited MUC4 promoter activity and endogenous MUC4 protein expression. In conclusion, we reported here a novel inhibitory element in the human MUC4 promoter. This provides additional data on MUC4 gene regulation and indicates that YY1 may be a potential target for abnormal MUC4 expression.