Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein
Open accessAbstract
Enhancer of Zeste [E(z)] is a Polycomb-group transcriptional repressor and one of the founding members of the family of SET domain-containing proteins. Several SET-domain proteins possess intrinsic histone methyltransferase (HMT) activity. However, recombinant E(z) protein was found to be inactive in a HMT assay. Here we report the isolation of a multiprotein E(z) complex that contains extra sex combs, suppressor of zeste-12 [Su(z)12], and the histone binding proteins RbAp46/RbAp48. This complex, which we termed Polycomb repressive complex (PRC) 2, possesses HMT activity with specificity for Lys 9 (K9) and Lys 27 (K27) of histone H3. The HMT activity of PRC2 is dependent on an intact SET domain in the E(z) protein. We hypothesize that transcriptional repression by the E(z) protein involves methylation-dependent recruitment of PRC1. The presence of Su(z)12, a strong suppressor of position effect variegation, in PRC2 suggests that PRC2 may play a widespread role in heterochromatin-mediated silencing.
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RBBP4 and RBBP7 are present in many protein complexes other than NuRD (Sin3 complex, PRC2).
“RBBP4 and RBBP7 are present in many protein complexes other than the NuRD complex (Sin3 complex, PRC2), which also could explain their observed dynamic behavior [21,22].”
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- Authors
- Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Reinberg, Danny
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-11-15
- Volume
- 16
- Issue
- 22
- Pages
- 2893-2905
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC187479
- OpenAlex
- W2165894156
- Cited by
- 1,596
- References
- 2
- Citations by year
- 2026: 30 · 2025: 39 · 2024: 34 · 2023: 57 · 2022: 77 · 2021: 73 · 2020: 63 · 2019: 90 · 2018: 64 · 2017: 88 · 2016: 72 · 2015: 74 · 2014: 93 · 2013: 69 · 2012: 76
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (P30 CA08748)
- Universiteit van Amsterdam
- National Institutes of Health (CA08748, GM-37120)
- National Cancer Institute (P30-CA-08748, CA08748, P30CA008748)
- National Institute of General Medical Sciences (GM37120, R01GM037120, R37GM037120)
- 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 › Cancer-related gene regulation
- Keywords
- Enhancer of zeste, polycomb repressive complex 2, histone methyltransferase activity, SET domain, histone H3 lysine 9 methylation, histone H3 lysine 27 methylation, transcriptional repression, heterochromatin silencing, position effect variegation, Polycomb group proteins
- MeSH terms
- Histone Methyltransferases, Amino Acid Sequence, Carrier Proteins, HeLa Cells, Histone Deacetylases, Histones, Humans, Lysine, Methyltransferases, Molecular Sequence Data, Nuclear Proteins, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Repressor Proteins, Substrate Specificity, Sequence Homology, Amino Acid, Drosophila Proteins, Macromolecular Substances, Multiprotein Complexes, Histone Deacetylase 1, Retinoblastoma-Binding Protein 4, Retinoblastoma-Binding Protein 7, Polycomb Repressive Complex 1, Polycomb Repressive Complex 2
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