title: An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B.
abstract: Covalent modifications of histone tails play important roles in gene transcription and silencing. We recently identified an ERG ( ets -related gene)-associated protein with a SET (suppressor of variegation, enhancer of zest and trithorax) domain (ESET) that was found to have the activity of a histone H3-specific methyltransferase. In the present study, we investigated the interaction of ESET with other chromatin remodelling factors. We show that ESET histone methyltransferase associates with histone deacetylase 1 (HDAC1) and HDAC2, and that ESET also interacts with the transcription co-repressors mSin3A and mSin3B. Deletion analysis of ESET reveals that an N-terminal region containing a tudor domain is responsible for interaction with mSin3A/B and association with HDAC1/2, and that truncation of ESET enhances its binding to mSin3. When bound to a promoter, ESET represses the transcription of a downstream luciferase reporter gene. This repression by ESET is independent of its histone methyltransferase activity, but correlates with its binding to the mSin3 co-repressors. In addition, the repression can be partially reversed by treatment with the HDAC inhibitor trichostatin A. Taken together, these data suggest that ESET histone methyltransferase can form a large, multi-protein complex(es) with mSin3A/B co-repressors and HDAC1/2 that participates in multiple pathways of transcriptional repression.
authors.affiliation: Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, USA. lyang@u.washington.edu
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Mei
authors.forename: Anna
authors.initials: A
authors.lastname: Zielinska-Kwiatkowska
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Matsui
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blackburn
authors.forename: Daniel
authors.initials: D
authors.lastname: Benedetti
authors.forename: Anton A
authors.initials: AA
authors.lastname: Krumm
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Taborsky
authors.forename: Howard A
authors.initials: HA
authors.lastname: Chansky
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011994:Recombinant Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C492042:SIN3B protein, human; C115812:Sin3b protein, mouse; D014157:Transcription Factors; C012589:trichostatin A; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C110550:HDAC1 protein, human; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex