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.
Skip Nav Destination
Article navigation
February 2003
- PDF Icon PDF LinkFront Matter
Research Article|
February 01 2003
An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B
Liu YANG;
Liu YANG
1
∗Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
†Division of Hematology, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
1To whom correspondence should be addressed, at Departments of Orthopedics and Medicine/Hematology (e-mail lyang@u.washington.edu).
Search for other works by this author on:
Qi MEI;
Qi MEI
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
§Division of Endocrinology, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
Search for other works by this author on:
Anna ZIELINSKA-KWIATKOWSKA;
Anna ZIELINSKA-KWIATKOWSKA
∗Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
Search for other works by this author on:
Yoshito MATSUI;
Yoshito MATSUI
∗Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
Search for other works by this author on:
Michael L. BLACKBURN;
Michael L. BLACKBURN
∗Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
Search for other works by this author on:
Daniel BENEDETTI;
Daniel BENEDETTI
∗Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
Search for other works by this author on:
Anton A. KRUMM;
Anton A. KRUMM
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
∥Division of Oncology, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
Search for other works by this author on:
Gerald J. TABORSKY, Jr;
Gerald J. TABORSKY, Jr
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
§Division of Endocrinology, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
Search for other works by this author on:
Howard A. CHANSKY
Howard A. CHANSKY
∗Department of Orthopedics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.
‡Medical Research Service, VA Puget Sound Health Care System, Seattle, WA 98108, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 31 2002
Revision Received:
October 11 2002
Accepted:
October 24 2002
Accepted Manuscript online:
October 24 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 369 (3): 651–657.
Article history
Received:
May 31 2002
Revision Received:
October 11 2002
Accepted:
October 24 2002
Accepted Manuscript online:
October 24 2002
Citation
Liu YANG, Qi MEI, Anna ZIELINSKA-KWIATKOWSKA, Yoshito MATSUI, Michael L. BLACKBURN, Daniel BENEDETTI, Anton A. KRUMM, Gerald J. TABORSKY, Howard A. CHANSKY; An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B. Biochem J 1 February 2003; 369 (3): 651–657. doi: https://doi.org/10.1042/bj20020854
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.