Steinberg XP, Hepp MI, Fernandez Garcia Y, Suganuma T, Swanson SK, Washburn M, Workman JL, Gutierrez JL

Transcription factor C/EBPβ 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/EBPβ protein is found as three major isoforms, C/EBPβ1, -2, and -3. They ...

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are generated by translation at alternative AUG initiation codons of a unique mRNA, C/EBPβ1 being the full-length isoform. It has been found that C/EBPβ1 participates in terminal differentiation processes. Conversely, C/EBPβ2 and -3 promote cell proliferation and are involved in malignant progression in a number of tissues. The mechanisms by which C/EBPβ2 and -3 promote cell proliferation and tumor progression are not fully understood. In this work, we sought to identify proteins interacting with hC/EBPβ 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-protein interaction studies confirmed this finding and also showed that hC/EBPβ directly interacts with hACF1. By overexpressing hC/EBPβ, hSNF2H, and hACF1 in HepG2 cells and analyzing variations in expression of cyclin D1 and other C/EBPβ target genes, we observed a functional interaction between C/EBPβ and SNF2H/ACF1, characterized mainly by suppression of C/EBPβ 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/EBPβ, hSNF2H, and hACF1 on the promoter region of this gene.

Date: Feb. 07, 2012

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