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

Transcription factor C/EBP beta 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 beta protein is found as three major isoforms, C/EBP beta 1, -2, and -3. They are generated by translation at alternative AUG initiation codons of a unique mRNA, C/EBP beta 1 being the full-length isoform. It has been found that C/EBP beta 1 participates in terminal differentiation processes. Conversely, C/EBP beta 2 and -3 promote cell proliferation and are involved in malignant progression in a number of tissues. The mechanisms by which C/EBP beta 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 beta 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/EBP beta directly interacts with hACF1. By overexpressing hC/EBP beta hSNF2H, and hACF1 in HepG2 cells and analyzing variations in expression of cyclin D1 and other C/EBP beta target genes, we observed a functional interaction between C/EBP beta and SNF2H/ACF1, characterized mainly by suppression of C/EBP beta 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 beta hSNF2H, and hACF1 on the promoter region of this gene.