title: Human CCAAT/enhancer-binding protein β interacts with chromatin remodeling complexes of the imitation switch subfamily.
abstract: 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 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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Concepción, Barrio Universitario s/n, Concepción, Chile 4070043.
authors.forename: Ximena P
authors.initials: XP
authors.lastname: Steinberg
authors.forename: Matias I
authors.initials: MI
authors.lastname: Hepp
authors.forename: Yaiza
authors.initials: Y
authors.lastname: Fernández García
authors.forename: Tamaki
authors.initials: T
authors.lastname: Suganuma
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Michael
authors.initials: M
authors.lastname: Washburn
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.forename: José L
authors.initials: JL
authors.lastname: Gutiérrez
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism; D005812:Genes, Switch; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: C411647:A1CF protein, human; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C452851:RSF1 protein, human; D012097:Repressor Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human