Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation.
Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation.
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Tet介导的RNA羟甲基胞嘧啶在小鼠ES细胞和分化过程中的功能作用
DOI：
10.1038/s41467-020-18729-6
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发表时间：
2020-10-02
影响因子：
16.6
通讯作者：
Fuks F
中科院分区：
文献类型：
--
作者：
Lan J;Rajan N;Bizet M;Penning A;Singh NK;Guallar D;Calonne E;Li Greci A;Bonvin E;Deplus R;Hsu PJ;Nachtergaele S;Ma C;Song R;Fuentes-Iglesias A;Hassabi B;Putmans P;Mies F;Menschaert G;Wong JJL;Wang J;Fidalgo M;Yuan B;Fuks F
Tet-enzyme介导的DNA中胞嘧啶的5-羟甲基化在小鼠胚胎干细胞（ESCs）中起着至关重要的作用。在RNA中，5-羟甲基胞嘧啶（5 hmC）最近也被证实，但其生理作用仍然是未知的。在这里，我们展示了这个标记在小鼠胚胎干细胞和分化胚状体中的作用和功能。ESCs中的转录组范围映射揭示了数百个由5 hmC标记的信使RNA，其特征在于定义的独特共有序列和特定特征。在分化过程中，大量的转录本，包括许多编码关键的多能性相关因子（如Eed和Jarid 2），显示出降低的胞嘧啶羟甲基化。使用Tet-knockout ESCs，我们发现泰特酶是mRNA中5 hmC沉积的部分原因。转录组范围内的搜索进一步揭示了Tet 1和Tet 2结合的mRNA靶点，其位点显示出与5 hmC位点相似的拓扑结构。Tet-mediated RNA羟甲基化被发现降低了关键的多能性促进转录本的稳定性。我们认为Tets引起的RNA胞嘧啶5-羟甲基化是转录组灵活性的标志，与多能性和谱系承诺之间的平衡密不可分。泰特介导的RNA羟甲基化（5 hmC）在哺乳动物中已被检测到，但其生理作用尚不清楚。在这里，作者绘制了胚胎干细胞（ESC）分化过程中的5 hmC，发现Tet-mediated RNA羟甲基化降低了关键多能性相关转录物的稳定性。
Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs reveals hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), show decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we find Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further reveals mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation is found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment. TET mediated RNA-hydroxymethylation (5hmC) has been detected in mammals, but its physiological role remains unclear. Here the authors map 5hmC during embryonic stem cell (ESC) differentiation and find that Tet-mediated RNA hydroxymethylation reduces the stability of crucial pluripotency related transcripts.
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影响因子：
12.3
作者：
Amort T;Rieder D;Wille A;Khokhlova-Cubberley D;Riml C;Trixl L;Jia XY;Micura R;Lusser A
通讯作者：
Lusser A
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
21.3
作者：
Etchegaray JP;Chavez L;Huang Y;Ross KN;Choi J;Martinez-Pastor B;Walsh RM;Sommer CA;Lienhard M;Gladden A;Kugel S;Silberman DM;Ramaswamy S;Mostoslavsky G;Hochedlinger K;Goren A;Rao A;Mostoslavsky R
通讯作者：
Mostoslavsky R
影响因子：
23.9
作者：
Fidalgo, Miguel;Huang, Xin;Guallar, Diana;Sanchez-Priego, Carlos;Valdes, Victor Julian;Saunders, Arven;Ding, Junjun;Wu, Wen-Shu;Clavel, Carlos;Wang, Jianlong
通讯作者：
Wang, Jianlong
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