Human CCAAT/Enhancer-Binding Protein 尾 Interacts with Chromatin Remodeling Complexes of the Imitation Switch Subfamily

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• 作者：Ximena P. Steinberg ; Matias I. Hepp ; Yaiza Fern谩ndez Garc铆a ; Tamaki Suganuma ; Selene K. Swanson ; Michael Washburn ; Jerry L. Workman ; Jos茅 L. Guti茅rrez
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：February 7, 2012
• 年：2012
• 卷：51
• 期：5
• 页码：952-962
• 全文大小：405K
• 年卷期：v.51,no.5(February 7, 2012)
• ISSN：1520-4995

文摘

Transcription factor C/EBP尾 is involved in several cellular processes, such as proliferation, differentiation, and energy metabolism. This factor exerts its activity through recruitment of different proteins or protein complexes, including the ATP-dependent chromatin remodeling complex SWI/SNF. The C/EBP尾 protein is found as three major isoforms, C/EBP尾1, -2, and -3. They are generated by translation at alternative AUG initiation codons of a unique mRNA, C/EBP尾1 being the full-length isoform. It has been found that C/EBP尾1 participates in terminal differentiation processes. Conversely, C/EBP尾2 and -3 promote cell proliferation and are involved in malignant progression in a number of tissues. The mechanisms by which C/EBP尾2 and -3 promote cell proliferation and tumor progression are not fully understood. In this work, we sought to identify proteins interacting with hC/EBP尾 using a proteomics approach. We found that all three isoforms interact with hSNF2H and hACF, components of ACF and CHRAC chromatin remodeling complexes, which belong to the imitation switch subfamily. Additional protein鈥損rotein interaction studies confirmed this finding and also showed that hC/EBP尾 directly interacts with hACF1. By overexpressing hC/EBP尾, hSNF2H, and hACF1 in HepG2 cells and analyzing variations in expression of cyclin D1 and other C/EBP尾 target genes, we observed a functional interaction between C/EBP尾 and SNF2H/ACF1, characterized mainly by suppression of C/EBP尾 transactivation activity in the presence of SNF2H and ACF1. Consistent with these findings, induction of differentiation of HepG2 cells by 1% DMSO was accompanied by a reduction in the level of cyclin D1 expression and the appearance of hC/EBP尾, hSNF2H, and hACF1 on the promoter region of this gene.