Cabin1 represses MEF2 transcriptional activity by association with a methyltransferase, SUV39H1.
Myocyte enhancer factor 2 (MEF2) plays pivotal roles in various biological processes, and its transcriptional activity is regulated by histone acetylation/deacetylation enzymes in a calcium-dependent fashion. A calcineurin-binding protein 1 (Cabin1) has been shown to participate in repression of MEF2 by recruiting mSin3 and its associated histone deacetylases. Here, we report that histone methylation also takes a part in Cabin1-mediated repression of MEF2. Immunoprecipitate of Cabin1 complex can methylate histone H3 by association with SUV39H1. SUV39H1 increased Cabin1-mediated repression of MEF2 transcriptional activity in MEF2-targeting promoters. The SUV39H1 was revealed to bind to the 501-900-amino acid region of Cabin1, which was distinct from its histone deacetylase-recruiting domain. In addition, the Gal4-Cabin1-(501-900) alone repressed a constitutively active Gal4-tk-promoter, indicating that Cabin1 recruits SUV39H1 and represses transcriptional activity. Finally, both SUV39H1 and Cabin1 were shown to bind on the MEF2 target promoter in a calcium-dependent manner. Thus, Cabin1 recruits chromatin-modifying enzymes, both histone deacetylases and a histone methyltransferase, to repress MEF2 transcriptional activity.
Jang
Hyonchol
H
Department of Biochemistry and Molecular Biology, Cancer Research Institute, Interdisciplinary Program in Genetic Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Choi
Doo-Eun
DE
Kim
Hyungsoo
H
Cho
Eun-Jung
EJ
Youn
Hong-Duk
HD
D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011496:Protein Methyltransferases; D014158:Transcription, Genetic / Q000235:genetics*
D000596:Amino Acids; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D010750:Phosphoproteins; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D002118:Calcium