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Publication : Sex-specific chromatin remodelling safeguards transcription in germ cells.

First Author  Huang TC Year  2021
Journal  Nature Volume  600
Issue  7890 Pages  737-742
PubMed ID  34880491 Mgi Jnum  J:326085
Mgi Id  MGI:7287976 Doi  10.1038/s41586-021-04208-5
Citation  Huang TC, et al. (2021) Sex-specific chromatin remodelling safeguards transcription in germ cells. Nature 600(7890):737-742
abstractText  Stability of the epigenetic landscape underpins maintenance of the cell-type-specific transcriptional profile. As one of the main repressive epigenetic systems, DNA methylation has been shown to be important for long-term gene silencing; its loss leads to ectopic and aberrant transcription in differentiated cells and cancer(1). The developing mouse germ line endures global changes in DNA methylation in the absence of widespread transcriptional activation. Here, using an ultra-low-input native chromatin immunoprecipitation approach, we show that following DNA demethylation the gonadal primordial germ cells undergo remodelling of repressive histone modifications, resulting in a sex-specific signature in mice. We further demonstrate that Polycomb has a central role in transcriptional control in the newly hypomethylated germline genome as the genetic loss of Ezh2 leads to aberrant transcriptional activation, retrotransposon derepression and dramatic loss of developing female germ cells. This sex-specific effect of Ezh2 deletion is explained by the distinct landscape of repressive modifications observed in male and female germ cells. Overall, our study provides insight into the dynamic interplay between repressive chromatin modifications in the context of a developmental reprogramming system.
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