G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis
Abstract
Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and in early embryonic cells, where it has been shown to be important for maintaining pluripotency. Following implantation, this gene undergoes a novel multi-step programme of inactivation. Transcriptional repression is followed by a pronounced increase in histone H3 methylation on Lys 9 that is mediated by the SET-containing protein, G9a. This step sets the stage for local heterochromatinization via the binding of HP1 and is required for subsequent de novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 re-expression, thereby preventing reprogramming.
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Development is fundamentally irreversible, providing a strong analogy for the irreversible changes that churn during chromosome and genome evolution.
“Interestingly, development is fundamentally irreversible (181–183), providing a strong analogy for the irreversible changes that churn during chromosome and genome evolution.”
From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [183]
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- Authors
- Feldman, N., Gerson, A., Fang, J., Li, E., Zhang, Y., Shinkai, Y., Cedar, H., & Bergman, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- University of North Carolina at Chapel Hill (US)
- Massachusetts General Hospital (US)
- Kyoto University (JP)
- Corresponding author
- Bergman, Yehudit
- Venue
- Nature Cell Biology
- Published
- 2006-01-15
- Volume
- 8
- Issue
- 2
- Pages
- 188-194
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2045619208
- Cited by
- 651
- References
- 0
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 10 · 2023: 15 · 2022: 16 · 2021: 17 · 2020: 27 · 2019: 19 · 2018: 29 · 2017: 29 · 2016: 27 · 2015: 35 · 2014: 39 · 2013: 52 · 2012: 71
- FWCI
- 15.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- 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
- Oct-3/4, G9a, histone H3 lysine 9 methylation, epigenetic silencing, pluripotency, early embryonic development, heterochromatinization, HP1, DNA methylation, DNMT3A, DNMT3B, transcriptional repression, reprogramming, implantation
- MeSH terms
- Nanog Homeobox Protein, DNA (Cytosine-5-)-Methyltransferase 1, Histone Methyltransferases, DNA Methyltransferase 3A, Chromobox Protein Homolog 5, DNA Methyltransferase 3B, Acetylation, Animals, Cell Differentiation, Chromosomal Proteins, Non-Histone, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Embryo, Mammalian, Fibroblasts, Heterochromatin, Histones, Methylation, Models, Genetic, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Tretinoin, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, DNA Methylation, Epigenesis, Genetic, Cell Line, Tumor, Embryonic Development, Chromatin Immunoprecipitation, Octamer Transcription Factor-3, Mice
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