Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development.
Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development.
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DOI：
10.1016/j.devcel.2012.12.015
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发表时间：
2013-02-11
影响因子：
11.8
通讯作者：
Jaenisch, Rudolf
中科院分区：
文献类型：
--
作者：
Dawlaty, Meelad M.;Breiling, Achim;Le, Thuc;Raddatz, Guenter;Barrasa, M. Inmaculada;Cheng, Albert W.;Gao, Qing;Powell, Benjamin E.;Li, Zhe;Xu, Mingjiang;Faull, Kym F.;Lyko, Frank;Jaenisch, Rudolf
泰特酶（Tet 1/2/3）在各种胚胎和成体组织中将5-甲基胞嘧啶（5 mC）转化为5-羟甲基胞嘧啶（5 hmC）。Tet 1或Tet 2的小鼠突变体是可行的，这提出了这些酶在发育中是否有重叠作用的问题。在这里，我们已经产生了Tet 1和Tet 2双敲除（DKO）ESC和小鼠。DKO ESC保持多能性，但耗尽了5 hmC并导致嵌合胚胎的发育缺陷。虽然一部分双突变胚胎表现出妊娠中期异常与围产期致死，可行的和明显正常的Tet 1/Tet 2缺陷小鼠也获得。DKO小鼠的5 hmC水平降低，5 mC水平升高，各种印迹基因座甲基化异常。然而，两种性别的动物都具有生育能力，雌性动物卵巢较小，生育能力降低。我们的数据表明，这两种酶的损失是兼容的发展，但促进超甲基化和妥协印迹。这也表明Tet 3在发育过程中对5 mC的羟基化有显著贡献。
Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in various embryonic and adult tissues. Mice mutant for either Tet1 or Tet2 are viable raising the question whether these enzymes have overlapping roles in development. Here, we have generated Tet1 and Tet2 double knockout (DKO) ESCs and mice. DKO ESCs remained pluripotent, but were depleted of 5hmC and caused developmental defects in chimeric embryos. While a fraction of double mutant embryos exhibited mid-gestation abnormalities with perinatal lethality, viable and overtly normal Tet1/Tet2 deficient mice were also obtained. DKO mice had reduced 5hmC and increased 5mC levels and abnormal methylation at various imprinted loci. Nevertheless, animals of both sexes were fertile with females having smaller ovaries and reduced fertility. Our data show that loss of both enzymes is compatible with development but promotes hypermethylation and compromises imprinting. It also suggests a significant contribution of Tet3 to hydroxylation of 5mC during development.
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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：
50.3
作者：
Moran-Crusio K;Reavie L;Shih A;Abdel-Wahab O;Ndiaye-Lobry D;Lobry C;Figueroa ME;Vasanthakumar A;Patel J;Zhao X;Perna F;Pandey S;Madzo J;Song C;Dai Q;He C;Ibrahim S;Beran M;Zavadil J;Nimer SD;Melnick A;Godley LA;Aifantis I;Levine RL
通讯作者：
Levine RL
DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tahiliani M;Koh KP;Shen Y;Pastor WA;Bandukwala H;Brudno Y;Agarwal S;Iyer LM;Liu DR;Aravind L;Rao A
通讯作者：
Rao A
影响因子：
4.8
作者：
Markoulaki, Styliani;Meissner, Alexander;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
64.5
作者：
Bernstein, BE;Mikkelsen, TS;Lander, ES
通讯作者：
Lander, ES