Biochemical Journal

Research article

An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B

Liu YANG, Qi MEI, Anna ZIELINSKA-KWIATKOWSKA, Yoshito MATSUI, Michael L. BLACKBURN, Daniel BENEDETTI, Anton A. KRUMM, Gerald J. TABORSKY Jr, Howard A. CHANSKY

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.

  • chromatin
  • ERG-associated protein with a SET domain (ESET)
  • SETDB1
  • trichostatin A
  • tudor domain

Footnotes

  • Abbreviations used: ERG, ets-related gene; ESET, ERG-associated protein with a SET domain (also called SETDB1); HDAC, histone deacetylase; PAH2, paired amphipathic helix 2; Rb, retinoblastoma protein; RbAp, retinoblastoma protein-associated protein; SET, suppressor of variegation, enhancer of zest and trithorax; SMN, survival of motor neurons; TSA, trichostatin A.