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.
Van Rechem
Capucine
C
CNRS UMR 8161, Institut de Biologie de LILLE, Université de Lille Nord de FRANCE, Institut PASTEUR de LILLE, IFR 142, 1 Rue Calmette, 59017 LILLE Cedex, France.
Boulay
Gaylor
G
Leprince
Dominique
D
D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D021122:Protein Subunits; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins