Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion.
Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion.
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DOI：
10.1016/j.molcel.2013.01.032
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发表时间：
2013-03-28
期刊：
影响因子：
16
通讯作者：
Fisher, Amanda G.
中科院分区：
文献类型：
--
作者：
Piccolo, Francesco M.;Bagci, Hakan;Brown, Karen E.;Landeira, David;Soza-Ried, Jorge;Feytout, Amelie;Mooijman, Dylan;Hajkova, Petra;Leitch, Harry G.;Tada, Takashi;Kriaucionis, Skirmantas;Dawlaty, Meelad M.;Jaenisch, Rudolf;Merkenschlager, Matthias;Fisher, Amanda G.
基因组印记根据其亲本起源指导基因座的等位基因特异性标记和表达。印记控制区（ICR）的差异DNA甲基化是在配子中建立的，尽管在发育过程中大部分保留下来，但可以通过将体细胞与胚胎生殖细胞（EGC）系融合来通过实验重置。在这里，我们证明了 10-11 易位蛋白 Tet1 和 Tet2 参与了该模型系统中印记的有效擦除。 B 细胞与 EGC 的融合启动多能重编程，其中 Oct4 的快速重新表达伴随着 5-羟甲基胞嘧啶 (5hmC) 在多个 ICR 处的积累。 Tet2 是 EGC 有效重编程能力所必需的，而 Tet1 是在 ICR 处特异性诱导 5-甲基胞嘧啶氧化所必需的。这些数据表明，Tet1 和 Tet2 蛋白在体细胞中细胞融合介导的多能重编程和印记擦除中具有不同的作用。 ► EGC 可以在融合后消除体细胞 ICR 处的 DNA 甲基化 ► EGC 选择性诱导体细胞基因组中 ICR 处的 5hmC 积累 ► 在这些印记结构域将 5mC 转化为 5hmC 需要 Tet1 ► Tet2 耗尽导致 EGC 延迟重编程
Genomic imprinting directs the allele-specific marking and expression of loci according to their parental origin. Differential DNA methylation at imprinted control regions (ICRs) is established in gametes and, although largely preserved through development, can be experimentally reset by fusing somatic cells with embryonic germ cell (EGC) lines. Here, we show that the Ten-Eleven Translocation proteins Tet1 and Tet2 participate in the efficient erasure of imprints in this model system. The fusion of B cells with EGCs initiates pluripotent reprogramming, in which rapid re-expression of Oct4 is accompanied by an accumulation of 5-hydroxymethylcytosine (5hmC) at several ICRs. Tet2 was required for the efficient reprogramming capacity of EGCs, whereas Tet1 was necessary to induce 5-methylcytosine oxidation specifically at ICRs. These data show that the Tet1 and Tet2 proteins have discrete roles in cell-fusion-mediated pluripotent reprogramming and imprint erasure in somatic cells. ► EGCs can erase DNA methylation at ICRs in somatic cells after fusion ► EGCs selectively induce 5hmC accumulation at ICRs in the somatic genome ► Conversion of 5mC to 5hmC at these imprinted domains requires Tet1 ► Tet2 depletion results in delayed reprogramming by EGCs
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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：
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：
16
作者：
Kallin, Eric M.;Rodriguez-Ubreva, Javier;Christensen, Jesper;Cimmino, Luisa;Aifantis, Iannis;Helin, Kristian;Ballestar, Esteban;Graf, Thomas
通讯作者：
Graf, Thomas
胚胎干细胞通过双相重编程在体细胞融合中诱导多能性。
影响因子：
16
作者：
Foshay KM;Looney TJ;Chari S;Mao FF;Lee JH;Zhang L;Fernandes CJ;Baker SW;Clift KL;Gaetz J;Di CG;Xiang AP;Lahn BT
通讯作者：
Lahn BT
影响因子：
64.5
作者：
Guo JU;Su Y;Zhong C;Ming GL;Song H
通讯作者：
Song H