Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation
Open accessAbstract
ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation.
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HDACs 1, 2 and 3 require association with large multisubunit corepressor complexes for maximal activity.
“HDACs 1, 2 and 3 require association with large multisubunit corepressor complexes for maximal activity7-12.”
From Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate (2012) · cites this paper as [7]
The Abstract identifies HDAC1 and HDAC2 as components of the multisubunit Sin3 and NuRD complexes. Table 1 and the section on NuRD and DNA methylation show that adding MTA2 markedly increases the activity of an HDAC1/HDAC2-containing core complex. The paper does not establish the same requirement for HDAC3, so the claim extends beyond its findings. (LLM, conf=0.88)
Experimental — accuracy not yet measuredmSin3A, SMRT, and N-CoR are part of large histone deacetylase complexes.
“The last three factors are part of the large histone deacetylase complexes (20, 51, 60).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [60]
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- Authors
- Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., & Reinberg, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of North Carolina at Chapel Hill (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Reinberg, D.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-08-01
- Volume
- 13
- Issue
- 15
- Pages
- 1924-1935
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC316920
- OpenAlex
- W2014817033
- Cited by
- 1,103
- References
- 69
- Citations by year
- 2026: 21 · 2025: 15 · 2024: 15 · 2023: 18 · 2022: 22 · 2021: 20 · 2020: 29 · 2019: 32 · 2018: 33 · 2017: 28 · 2016: 40 · 2015: 42 · 2014: 54 · 2013: 60 · 2012: 43
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Wellcome Trust
- Darwin Trust of Edinburgh
- National Institutes of Health (2r01gm048518-05)
- National Cancer Institute
- National Institute of General Medical Sciences (F32GM019515, GM-48518, 1F32GM19515-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- 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
- Keywords
- NuRD complex, HDAC1, HDAC2, RbAp48, MTA2, MBD3, MBD2, DNA methylation, nucleosome remodeling, histone acetylation, gene silencing, chromatin remodeling
- MeSH terms
- Adenosine Triphosphatases, Amino Acid Sequence, Autoantigens, Base Sequence, Carrier Proteins, Cloning, Molecular, DNA, DNA Helicases, DNA-Binding Proteins, HeLa Cells, Histone Deacetylases, Humans, Molecular Sequence Data, Multienzyme Complexes, Nuclear Proteins, Nucleosomes, Protein Binding, Recombinant Fusion Proteins, Repressor Proteins, Transcription Factors, Sequence Homology, Amino Acid, DNA Methylation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Histone Deacetylase 1, Histone Deacetylase 2, Retinoblastoma-Binding Protein 4, Retinoblastoma-Binding Protein 7
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