Chromatin dynamics during epigenetic reprogramming in the mouse germ line

By P. Hájková, K. Ancelin, T. Waldmann, N. Lacoste, U. Lange, F. Cesari, Caroline Lee, G. Almouzni, Robert Schneider, M. Surani. Nature, 2008

651 citations recorded by the source corpus.

A unique feature of the germ cell lineage is the generation of totipotency. A critical event in this context is DNA demethylation and the erasure of parental imprints in mouse primordial germ cells (PGCs) on embryonic day 11.5 (E11.5) after they enter into the developing gonads. Little is yet known about the mechanism involved, except that it is apparently an active process. We have examined the associated changes in the chromatin to gain further insights into this reprogramming event. Here we show that the chromatin changes occur in two steps. The first changes in nascent PGCs at E8.5 establish a distinctive chromatin signature that is reminiscent of pluripotency. Next, when PGCs are residing in the gonads, major changes occur in nuclear architecture accompanied by an extensive erasure of several histone modifications and exchange of histone variants. Furthermore, the histone chaperones HIRA and NAP-1 (NAP111), which are implicated in histone exchange, accumulate in PGC nuclei undergoing reprogramming. We therefore suggest that the mechanism of histone replacement is critical for these chromatin rearrangements to occur. The marked chromatin changes are intimately linked with genome-wide DNA demethylation. On the basis of the timing of the observed events, we propose that if DNA demethylation entails a DNA repair-based mechanism, the evident histone replacement would represent a repair-induced response event rather than being a prerequisite.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bda93c5926041898ed111c30f4a285d743a02b9d

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Citations in the corpus

Induced pluripotency: history, mechanisms, and applications. (2010, background): “Evidence for a role of active DNA demethylation during development comes from studies of germ cells (Hajkova et al. 2008, 2010) and zygotes (Mayer et al. 2000; Oswald et al. 2000) as well as some adult somatic cells, including neurons and T lymphocytes (Bruniquel and Schwartz 2003; Miller and…”
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