EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency
Open accessAbstract
Trimethylation on H3K27 (H3K27me3) mediated by Polycomb repressive complex 2 (PRC2) has been linked to embryonic stem cell (ESC) identity and pluripotency. EZH2, the catalytic subunit of PRC2, has been reported as the sole histone methyltransferase that methylates H3K27 and mediates transcriptional silencing. Analysis of Ezh2(-/-) ESCs suggests existence of an additional enzyme(s) catalyzing H3K27 methylation. We have identified EZH1, a homolog of EZH2 that is physically present in a noncanonical PRC2 complex, as an H3K27 methyltransferase in vivo and in vitro. EZH1 colocalizes with the H3K27me3 mark on chromatin and preferentially preserves this mark on development-related genes in Ezh2(-/-) ESCs. Depletion of Ezh1 in cells lacking Ezh2 abolishes residual methylation on H3K27 and derepresses H3K27me3 target genes, demonstrating a role of EZH1 in safeguarding ESC identity. Ezh1 partially complements Ezh2 in executing pluripotency during ESC differentiation, suggesting that cell-fate transitions require epigenetic specificity.
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The residual H3K27me3 deposition in H3.3K27M cells may result from residual EZH2 activity or continued EZH1-containing complex activity.
“Active deposition of the H3K27me3 mark at selected sites remains possible in H3.3K27M cells (Figure 8E; Figure S8D), possibly by residual EZH2 activity, as recently suggested (Mohammad et al., 2017), or by continued activity of EZH1-containing complexes (Shen et al., 2008).”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Shen et al., 2008
Active deposition of H3K27me3 at selected sites remains possible in H3.3K27M cells.
“Active deposition of the H3K27me3 mark at selected sites remains possible in H3.3K27M cells (Figure 8E; Figure S8D), possibly by residual EZH2 activity, as recently suggested (Mohammad et al., 2017), or by continued activity of EZH1-containing complexes (Shen et al., 2008).”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Shen et al., 2008
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- Authors
- Shen, X., Liu, Y., Hsu, Y.-J., Fujiwara, Y., Kim, J., Mao, X., Yuan, G.-C., & Orkin, S. H.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Orkin, Stuart H.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 32
- Issue
- 4
- Pages
- 491-502
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2630502
- OpenAlex
- W2116318886
- Cited by
- 1,021
- References
- 47
- Citations by year
- 2026: 26 · 2025: 56 · 2024: 44 · 2023: 41 · 2022: 54 · 2021: 81 · 2020: 51 · 2019: 70 · 2018: 59 · 2017: 72 · 2016: 52 · 2015: 68 · 2014: 72 · 2013: 68 · 2012: 62
- FWCI
- 19.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1719 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Dana-Farber Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- EZH1, EZH2, H3K27me3, polycomb repressive complex 2, pluripotency, histone methyltransferase, epigenetic regulation, cell fate transitions, transcriptional silencing
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Animals, Cell Differentiation, Cell Line, DNA-Binding Proteins, Genes, Regulator, Histones, Lysine, Methylation, Models, Biological, Histone-Lysine N-Methyltransferase, Stem Cells, Transcription Factors, Mice, Polycomb Repressive Complex 2
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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