Extensive and orderly
reprogramming of genome-wide chromatin modifications associated with specification
and early development of germ cells in mice
Seki Y, Hayashi K, Itoh K, Mizugaki M, Saitou M and Matsui Y
Dev Biol 278(2):440-458 (2005)
SUMMARY
Induction of mouse germ cells occurs from the proximal epiblast at around
embryonic day (E) 7.0. These germ cells then migrate to, and enter the
gonads at about E10.5 after which they undergo epigenetic reprogramming
including erasure of parental imprints. However, the epigenetic properties
acquired by nascent germ cells and the potential remodeling of these epigenetic
marks in the subsequent migratory period have been largely unexplored.
Here we have used immunohistochemistry to examine several genome-wide
epigenetic modifications occurring in germ cells from their specification
to their colonization of the genital ridges. We show that at around E8.0,
germ cells concomitantly and significantly reduce H3-K9 dimethylation
and DNA methylation, two major repressive modifications for gene expression.
These events are preceded by the transient loss of all the DNA methyltransferases
from their nuclei. By contrast, germ cells substantially increase the
levels of H3-K27 trimethylation, another repressive modification with
more plasticity, at E8.5-9.0 and maintain this state until at least E12.5.
H3-K4 methylation and H3-K9 acetylation, modifications associated with
transcriptionally permissive/active chromatin, are similar in germ and
surrounding somatic cells but germ cells transiently increase these marks
sharply upon their entry into the genital ridge. H3-K9 trimethylation,
a hallmark of centromeric heterochromatin, is kept relatively constant
during the periods examined. We suggest that this orderly and extensive
epigenetic reprogramming in premigratory and migratory germ cells might
be necessary for their reacquisition of underlying totipotency, for subsequent
specific epigenetic remodeling, including the resetting of parental imprints,
and for the production of gametes with an appropriate epigenotype for
supporting normal development.
LINK
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