Coupling Genome Defence to Epigenetic Reprogramming
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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.
