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Coupling Genome Defence to Epigenetic Reprogramming

Published: Thursday, September 06, 2012
Last Updated: Thursday, September 06, 2012
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The work, just published in Development, identifies genes DIRECTLY regulated by DNA methylation.

The promoters of these genes appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation in somatic cells. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing Transposable element activity in germ cells.

DNA methylation plays an important role in gene silencing and repressing transposable elements (TEs). During primordial germ cell (PGC) development, DNA methylation marks are erased during extensive epigenetic reprogramming, so how does this demethylation impact gene expression and TE repression in PGCs? Richard Meehan and co-workers show that DNA methylation at the promoters of germline-specific genes couples genome-defence mechanisms to epigenetic reprogramming in mouse PGCs. The researchers identify a set of germline-specific genes that are dependent exclusively on promoter DNA methylation for their silencing; their promoters possess specialised chromatin in somatic cells that does not acquire additional repressive histone modifications. This set, they discover, is enriched in genes involved in suppressing TE activity in germ cells, and the expression of these genes is activated during two phases of DNA demethylation in PGCs. These findings suggest that unique reliance on promoter DNA methylation acts as a highly tuned sensor of global DNA demethylation and allows PGCs to be primed to suppress TEs.

Hackett JA, Reddington JP, Nestor CE, Dunican DS, Branco MR, Reichmann J, Reik W, Surani MA, Adams IR, Meehan RR.
Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline.
Development. 2012 Oct;139(19):3623-32. PubMed PMID: 22949617.

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