Poly(ADP-ribosyl)ation acts in the DNA demethylation of mouse primordial germ cells also with DNA damage-independent roles.
Poly(ADP-ribosyl)ation acts in the DNA demethylation of mouse primordial germ cells also with DNA damage-independent roles.
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DOI：
10.1371/journal.pone.0046927
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Caiafa P
中科院分区：
文献类型：
--
作者：
Ciccarone F;Klinger FG;Catizone A;Calabrese R;Zampieri M;Bacalini MG;De Felici M;Caiafa P
聚（ADP-核糖基）化调节染色质结构和转录驱动表观遗传事件。特别是，Parp 1能够直接影响DNA甲基化模式，控制Dnmt 1的转录和活性。在这里，我们表明，ADP-核糖聚合物的水平和Parp 1的表达是显着高的小鼠原始生殖细胞（PGCs）时，大部分的DNA去甲基化发生在胚胎生殖系表观遗传重编程。值得注意的是，Parp 1活性在PGCs中被刺激，甚至在其参与与活性DNA去甲基化相关的DNA损伤反应之前。我们证明，PARP抑制损害PGCs的全基因组和基因座特异性DNA甲基化擦除。此外，我们的证据表明，PARP活性的损害导致Tet 1羟化酶参与主动DNA去甲基化的基因编码的表达显着减少。综上所述，这些结果表明，新的和辅助作用的聚（ADP-核糖基）化在生殖细胞DNA去甲基化，并建议其可能更普遍参与基因组重编程。
Poly(ADP-ribosyl)ation regulates chromatin structure and transcription driving epigenetic events. In particular, Parp1 is able to directly influence DNA methylation patterns controlling transcription and activity of Dnmt1. Here, we show that ADP-ribose polymer levels and Parp1 expression are noticeably high in mouse primordial germ cells (PGCs) when the bulk of DNA demethylation occurs during germline epigenetic reprogramming in the embryo. Notably, Parp1 activity is stimulated in PGCs even before its participation in the DNA damage response associated with active DNA demethylation. We demonstrate that PARP inhibition impairs both genome-wide and locus-specific DNA methylation erasure in PGCs. Moreover, we evidence that impairment of PARP activity causes a significant reduction of expression of the gene coding for Tet1 hydroxylases involved in active DNA demethylation. Taken together these results demonstrate new and adjuvant roles of poly(ADP-ribosyl)ation during germline DNA demethylation and suggest its possible more general involvement in genome reprogramming.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
DOI：
10.1074/jbc.m801170200
发表时间：
2008-08-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Guastafierro T;Cecchinelli B;Zampieri M;Reale A;Riggio G;Sthandier O;Zupi G;Calabrese L;Caiafa P
通讯作者：
Caiafa P
影响因子：
5.6
作者：
Chevanne, Marta;Zampieri, Michele;Caiafa, Paola
通讯作者：
Caiafa, Paola
影响因子：
4.8
作者：
Fitzgerald, Megan E.;Drohat, Alexander C.
通讯作者：
Drohat, Alexander C.
DOI：
10.1126/science.1190614
发表时间：
2010-10-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng S;Jacobsen SE;Reik W
通讯作者：
Reik W