HIC1 interacts with a specific subunit of SWI/SNF complexes, ARID1A/BAF250A.
HIC1, a tumor suppressor gene epigenetically silenced in many human cancers encodes a transcriptional repressor involved in regulatory loops modulating p53-dependent and E2F1-dependent cell survival and stress responses. HIC1 is also implicated in growth control since it recruits BRG1, one of the two alternative ATPases (BRM or BRG1) of SWI/SNF ... chromatin-remodeling complexes to repress transcription of E2F1 in quiescent fibroblasts. Here, through yeast two-hybrid screening, we identify ARID1A/BAF250A, as a new HIC1 partner. ARID1A/BAF250A is one of the two mutually exclusive ARID1-containing subunits of SWI/SNF complexes which define subsets of complexes endowed with anti-proliferative properties. Co-immunoprecipitation assays in WI38 fibroblasts and in BRG1-/- SW13 cells showed that endogenous HIC1 and ARID1A proteins interact in a BRG1-dependent manner. Furthermore, we demonstrate that HIC1 does not interact with BRM. Finally, sequential chromatin immunoprecipitation (ChIP-reChIP) experiments demonstrated that HIC1 represses E2F1 through the recruitment of anti-proliferative SWI/SNF complexes containing ARID1A.
Mesh Terms:
Cell Line, Chromatin Immunoprecipitation, Down-Regulation, E2F1 Transcription Factor, Gene Expression Regulation, Neoplastic, Humans, Kruppel-Like Transcription Factors, Nuclear Proteins, Protein Subunits, Transcription Factors, Tumor Suppressor Proteins, Two-Hybrid System Techniques
Cell Line, Chromatin Immunoprecipitation, Down-Regulation, E2F1 Transcription Factor, Gene Expression Regulation, Neoplastic, Humans, Kruppel-Like Transcription Factors, Nuclear Proteins, Protein Subunits, Transcription Factors, Tumor Suppressor Proteins, Two-Hybrid System Techniques
Biochem. Biophys. Res. Commun.
Date: Aug. 07, 2009
PubMed ID: 19486893
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