AID deficiency interferes with genome-wide erasure of DNA methylation patterns

ppcl2

Wolf Reik是做X inactivation的牛人
9 w" g9 ^$ I  _& y' r2 c; I( sNature 463, 1101-1105 (25 February 2010) | doi:10.1038/nature08829; Received 24 November 2009; Accepted 15 January 2010; Published online 22 January 2010
% F. W8 z6 i0 X+ Chttp://www.nature.com/nature/jou ... ll/nature08829.html
& }6 o- o4 [2 Q& L9 MGenome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency* ~( s6 C  y: x  }" B" W
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Christian Popp1,5, Wendy Dean1,5, Suhua Feng2,5, Shawn J. Cokus2, Simon Andrews3, Matteo Pellegrini2, Steven E. Jacobsen2,4 & Wolf Reik14 t! i2 d3 ^1 `) E* J8 w. W& C
Epigenetic reprogramming including demethylation of DNA occurs in mammalian primordial germ cells (PGCs) and in early embryos, and is important for the erasure of imprints and epimutations, and the return to pluripotency1, 2, 3, 4, 5, 6, 7, 8, 9. The extent of this reprogramming and its molecular mechanisms are poorly understood. We previously showed that the cytidine deaminases AID and APOBEC1 can deaminate 5-methylcytosine in vitro and in Escherichia coli, and in the mouse are expressed in tissues in which demethylation occurs10. Here we profiled DNA methylation throughout the genome by unbiased bisulphite next generation sequencing11, 12, 13 in wild-type and AID-deficient mouse PGCs at embryonic day (E)13.5. Wild-type PGCs revealed marked genome-wide erasure of methylation to a level below that of methylation deficient (Np95-/-, also called Uhrf1-/-) embryonic stem cells, with female PGCs being less methylated than male ones. By contrast, AID-deficient PGCs were up to three times more methylated than wild-type ones; this substantial difference occurred throughout the genome, with introns, intergenic regions and transposons being relatively more methylated than exons. Relative hypermethylation in AID-deficient PGCs was confirmed by analysis of individual loci in the genome. Our results reveal that erasure of DNA methylation in the germ line is a global process, hence limiting the potential for transgenerational epigenetic inheritance. AID deficiency interferes with genome-wide erasure of DNA methylation patterns, indicating that AID has a critical function in epigenetic reprogramming and potentially in restricting the inheritance of epimutations in mammals.

caoninn

不错，PGC是个研究表观遗传的好材料！精子发育过程也是研究表观遗传的好材料。

saturn

最近关于DNA demethylation确实很热呀，AID 和DNA demethylation 的关系值得好好研究，+ F  Y7 I+ S) I6 B
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7 t' L* v, c1 I回复 2# caoninn

ppcl2

回复 3# saturn
2 }; `) D% B9 K) i$ kDNA demethylation是Epigenetics的下一个高潮！