Epigenetic resetting in the human germ line entails histone modification remodeling

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Epigenetic resetting in the human germ line entails histone modification remodeling
Title:
Epigenetic resetting in the human germ line entails histone modification remodeling
Journal Title:
Science Advances
Publication Date:
18 January 2023
Citation:
Gruhn, W. H., Tang, W. W. C., Dietmann, S., Alves-Lopes, J. P., Penfold, C. A., Wong, F. C. K., Ramakrishna, N. B., & Surani, M. A. (2023). Epigenetic resetting in the human germ line entails histone modification remodeling. Science Advances, 9(3). https://doi.org/10.1126/sciadv.ade1257
Abstract:
Epigenetic resetting in the mammalian germ line entails acute DNA demethylation, which lays the foundation for gametogenesis, totipotency, and embryonic development. We characterize the epigenome of hypomethylated human primordial germ cells (hPGCs) to reveal mechanisms preventing the widespread derepression of genes and transposable elements (TEs). Along with the loss of DNA methylation, we show that hPGCs exhibit a profound reduction of repressive histone modifications resulting in diminished heterochromatic signatures at most genes and TEs and the acquisition of a neutral or paused epigenetic state without transcriptional activation. Efficient maintenance of a heterochromatic state is limited to a subset of genomic loci, such as evolutionarily young TEs and some developmental genes, which require H3K9me3 and H3K27me3, respectively, for efficient transcriptional repression. Accordingly, transcriptional repression in hPGCs presents an exemplary balanced system relying on local maintenance of heterochromatic features and a lack of inductive cues.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This work was supported by the Wellcome Investigator Awards in Science 209475/Z/17/Z, the Wellcome Investigator Awards in Science 096738/Z/11/Z, the BBSRC research grant G103986, the Croucher Postdoctoral Research Fellowship, the Marie Skłodowska-Curie Actions- Individual Fellowship (836291: GERMINOID) from the European Commission, and the International Postdoc Fellowship (2019-06316) from the Swedish Research Council.
Description:
ISSN:
2375-2548
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