Cited by 444Genomics and Chromatin DynamicsHistone Deacetylase Inhibitors ResearchEstrogen and related hormone effects

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Purification and functional characterization of the human N‐CoR complex: the roles of HDAC3, TBL1 and TBLR1

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Yoon, Ho‐Geun, Chan, Doug W., Huang, Zhi‐Qing, Li, Jiwen, Fondell, Joseph D., Qin, Jun, Wong, Jiemin·2003·The EMBO Journal

DOI 10.1093/emboj/cdg120PMC PMC151047

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Abstract

Corepressors N-CoR and SMRT participate in diverse repression pathways and exist in large protein complexes including HDAC3, TBL1 and TBLR1. However, the roles of these proteins in SMRT-N-CoR complex function are largely unknown. Here we report the purification and functional characterization of the human N-CoR complex. The purified N-CoR complex contains 10-12 associated proteins, including previously identified components and a novel actin-binding protein IR10. We show that TBL1/TBLR1 associates with N-CoR through two independent interactions: the N-terminal region and the C-terminal WD-40 repeats interact with the N-CoR RD1 and RD4 region, respectively. In vitro, TBL1/TBLR1 bind histones H2B and H4, and, importantly, repression by TBL1/TBLR1 correlates with their interaction with histones. By using specific small interference RNAs (siRNAs), we demonstrate that HDAC3 is essential, whereas TBL1 and TBLR1 are functionally redundant but essential for repression by unliganded thyroid hormone receptor. Together, our data reveal the roles of HDAC3 and TBL/TBLR1 and provide evidence for the functional importance of histone interaction in repression mediated by SMRT-N-CoR complexes.

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Authors: Yoon, H., Chan, D. W., Huang, Z., Li, J., Fondell, J. D., Qin, J., & Wong, J.
Affiliations: Baylor College of Medicine (US)
Corresponding author: Wong, Jiemin
ORCID: Yoon, Ho‐Geun
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2003-03-17
Volume: 22
Issue: 6
Pages: 1336-1346
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/cdg120
PMC: PMC151047
OpenAlex: W1969097053
Cited by: 444
References: 42
Citations by year: 2026: 10 · 2025: 7 · 2024: 12 · 2023: 17 · 2022: 7 · 2021: 13 · 2020: 16 · 2019: 14 · 2018: 13 · 2017: 16 · 2016: 18 · 2015: 18 · 2014: 19 · 2013: 21 · 2012: 23
FWCI: 10.57
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK 58679, R01DK056324, R01DK058679, DK 56324)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: SMRT, HDAC3, TBL1, corepressors, transcriptional repression, histone interaction, histone H2B, histone H4, thyroid hormone receptor, actin-binding proteins, WD40 repeats, protein complex purification, functional redundancy
MeSH terms: Histone Deacetylase 3, Amino Acid Sequence, Cell Line, DNA-Binding Proteins, HeLa Cells, Histone Deacetylases, Histones, Humans, Microfilament Proteins, Nuclear Proteins, Peptide Fragments, Protein Binding, Receptors, Thyroid Hormone, Recombinant Proteins, Repressor Proteins, Transducin, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Protein Subunits, RNA, Small Interfering

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Purification and functional characterization of the human N‐CoR complex: the roles of HDAC3, TBL1 and TBLR1

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