Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

Yoo, Jung-Yoon; Choi, Kyung-Chul; Kang, HeeBum; Kim, Young Jun; Lee, Jeongmin; Jun, Woo Jin; Kim, Mi-Jeong; Lee, Yoo-Hyun; Lee, Ok-Hee; Yoon, Ho-Geun

doi:10.1016/j.febslet.2010.03.048

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Volume 584, Issue 11 , Pages 2225-2230, 3 June 2010

Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

Edited by Laszlo Nagy

Jung-Yoon Yoo
- Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
- Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
- These authors contributed equally to this work.
Kyung-Chul Choi
- Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
- Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
- These authors contributed equally to this work.
HeeBum Kang
- Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
- Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
Young Jun Kim
- Department of Food and Biotechnology, Korea University, Chungnam, South Korea
Jeongmin Lee
- Department of Medical Nutrition, Kyung Hee University, Kyunggi-do, 446-701, South Korea
Woo Jin Jun
- Department of Food and Nutrition, Chonnam National University, Gwangju, South Korea
Mi-Jeong Kim
- Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
- Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
Yoo-Hyun Lee
- Department of Food and Nutrition, The University of Suwon, South Korea
Ok-Hee Lee
- Severance Hospital Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, South Korea
Ho-Geun Yoon
- Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea
- Brain Korea 21 Project for Medical Sciences Korea, Yonsei University College of Medicine, South Korea
- Corresponding author at: Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, South Korea. Fax: +82 2 312 5041.

Received 29 January 2010; received in revised form 15 March 2010; accepted 31 March 2010. published online 12 April 2010.

Abstract

This is the first report that L(3)mbt-like 2 (L3MBTL2) specifically interacts with the histone deacetylase domain of histone deacetylase 3 (HDAC3) via its MBT domain. Here, we show that L3MBTL2 selectively interacts with HDAC3, but not other class I HDACs. An in vitro peptide-binding assay demonstrated the specific association of HDAC3 with methylated histone-K20 tail and L3MBTL2. Furthermore, depletion of HDAC3 resulted in a decrease of methylated K20-H4, as well as an increase in acetylated histone H3. Consequently, HDAC3 knock-down selectively suppressed L3MBTL2-mediated transcriptional repression. Taken together, our results reveal the concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression.

Structured summary

MINT-7719975: L3MBTL2 (uniprotkb:Q969R5) and HDAC3 (uniprotkb:O15379) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

MINT-7719941, MINT-7719921: L3MBTL2 (uniprotkb:Q969R5) binds (MI:0407) to HDAC3 (uniprotkb:O15379) by pull down (MI:0096)

MINT-7719991: HDAC3 (uniprotkb:O15379) physically interacts (MI:0915) with L3MBTL2 (uniprotkb:Q969R5) by anti bait coimmunoprecipitation (MI:0006)

MINT-7719958: L3MBTL2 (uniprotkb:Q969R5) physically interacts (MI:0915) with HDAC3 (uniprotkb:O15379) by anti tag coimmunoprecipitation (MI:0007)

MINT-7719897: HDAC3 (uniprotkb:O15379) physically interacts (MI:0915) with L3MBTL2 (uniprotkb:Q969R5) by two hybrid (MI:0018)

Abbreviations: L3MBTL2, L(3)mbt-like 2, HDAC3, histone deacetylase 3, HMT, histone methyltransferase, ChIP, chromatin immunoprecipitation

Keywords: L(3)mbt-like 2, Histone deacetylase 3, MBT domain, Transcription