Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells.
Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells.
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DOI：
10.1016/j.stem.2013.01.016
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发表时间：
2013-04-04
期刊：
影响因子：
23.9
通讯作者：
Clark, Amander T.
中科院分区：
文献类型：
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作者：
Vincent, John J.;Huang, Yun;Chen, Pao-Yang;Feng, Suhua;Calvopina, Joseph H.;Nee, Kevin;Lee, Serena A.;Thuc Le;Yoon, Alexander J.;Faull, Kym;Fan, Guoping;Rao, Anjana;Jacobsen, Steven E.;Pellegrini, Matteo;Clark, Amander T.
原始生殖细胞（PGCs）在胚胎发生过程中经历了巨大的甲基化重排，包括建立种系表观遗传基态的初始全基因组DNA去甲基化。5-甲基胞嘧啶（5 mC）双加氧酶Tet 1和Tet 2在初始全基因组DNA去甲基化过程中的作用尚未直接研究。使用从对照或Tet 2 −/−; Tet 1敲除胚胎干细胞（ESC）分化的PGC，我们表明体外PGC（iPGC）形成和全基因组DNA去甲基化不受Tet 1和Tet 2缺乏的影响，因此5-羟甲基胞嘧啶（5 hmC）。然而，许多启动子和基因体在突变iPGC中被高甲基化，这与5 hmC作为位点特异性去甲基化中间体的作用一致。总而言之，我们的研究结果支持了一个修正的PGC DNA去甲基化模型，其中第一阶段的全面5 mC损失不涉及5 hmC。相反，Tet 1和Tet 2在随后的发育过程中塑造PGC上位基因组中具有位点特异性作用。
Primordial germ cells (PGCs) undergo dramatic rearrangements to their methylome during embryo-genesis, including initial genome-wide DNA demethylation that establishes the germline epigenetic ground state. The role of the 5-methylcytosine (5mC) dioxygenases Tet1 and Tet2 in the initial genome-wide DNA demethylation process has not been examined directly. Using PGCs differentiated from either control or Tet2−/−; Tet1 knockdown embryonic stem cells (ESCs), we show that in vitro PGC (iPGC) formation and genome-wide DNA demethylation are unaffected by the absence of Tet1 and Tet2, and thus 5-hydroxymethylcytosine (5hmC). However, numerous promoters and gene bodies were hypermethylated in mutant iPGCs, which is consistent with a role for 5hmC as an intermediate in locus-specific demethylation. Altogether, our results support a revised model of PGC DNA demethylation in which the first phase of comprehensive 5mC loss does not involve 5hmC. Instead, Tet1 and Tet2 have a locus-specific role in shaping the PGC epige-nome during subsequent development.
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DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hackett JA;Sengupta R;Zylicz JJ;Murakami K;Lee C;Down TA;Surani MA
通讯作者：
Surani MA
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
影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E
DOI：
10.1007/978-1-61779-089-8_16
发表时间：
2011-01-01
期刊：
HIGH-THROUGHPUT NEXT GENERATION SEQUENCING: METHODS AND APPLICATION
影响因子：
--
作者：
Feng, Suhua;Rubbi, Liudmilla;Pellegrini, Matteo
通讯作者：
Pellegrini, Matteo