Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network.
Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network.
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染色质 lncRNA Platr10 通过协调染色体内调控网络来控制干细胞多能性
DOI：
10.1186/s13059-021-02444-6
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发表时间：
2021-08-19
期刊：
影响因子：
12.3
通讯作者：
Hu JF
中科院分区：
文献类型：
--
作者：
Du Z;Wen X;Wang Y;Jia L;Zhang S;Liu Y;Zhou L;Li H;Yang W;Wang C;Chen J;Hao Y;Salgado Figueroa D;Chen H;Li D;Chen N;Celik I;Zhu Y;Yan Z;Fu C;Liu S;Jiao B;Wang Z;Zhang H;Gülsoy G;Luo J;Qin B;Gao S;Kapranov P;Esteban MA;Zhang S;Li W;Ay F;Chen R;Hoffman AR;Cui J;Hu JF
核心干细胞因子基因的特定三维染色体内结构是将体细胞重编程为多能性所必需的。由于对策划这种结构重塑的表观遗传学读者知之甚少，我们使用了一种新型染色质RNA原位逆转录测序（CRIST-seq）方法来分析Oct 4启动子中的长链非编码RNA（lncRNA）。我们将Platr 10鉴定为在体细胞重编程中激活的Oct 4-Sox 2结合lncRNA。Platr 10对于维持多能性至关重要，缺乏这种lncRNA会导致干细胞退出多能性。在成纤维细胞中，异位表达的Platr 10反式激活核心干细胞因子基因并增强多能重编程。使用RNA逆转录相关陷阱测序（RAT-seq），我们发现Platr 10与多个多能性相关基因相互作用，包括Oct 4，Sox 2，Klf 4和c-Myc，这些基因已被广泛用于重编程体细胞。从机制上讲，我们证明Platr 10有助于协调染色体内启动子-增强子循环，并招募TET 1，TET 1是一种积极诱导DNA去甲基化以启动多能性的酶。我们进一步表明，Platr 10包含一个Oct 4结合元件，与Oct 4启动子和TET 1结合元件，招募TET 1相互作用。这两个元件中的任何一个的突变都会消除Platr 10的活性。这些数据表明，Platr 10作为一种新的染色质RNA分子，通过调节染色质结构和调节核心干细胞因子网络中的DNA甲基化来控制反式多能性。在线版本包含补充材料，可通过10.1186/s13059-021-02444-6获得。
A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in the Oct4 promoter. We identify Platr10 as an Oct4 - Sox2 binding lncRNA that is activated in somatic cell reprogramming. Platr10 is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressed Platr10 functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show that Platr10 interacts with multiple pluripotency-associated genes, including Oct4, Sox2, Klf4, and c-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate that Platr10 helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show that Platr10 contains an Oct4 binding element that interacts with the Oct4 promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishes Platr10 activity. These data suggest that Platr10 functions as a novel chromatin RNA molecule to control pluripotency in trans by modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network. The online version contains supplementary material available at 10.1186/s13059-021-02444-6.
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影响因子：
14
作者：
Chen M;Zhang H;Wu J;Xu L;Xu D;Sun J;He Y;Zhou X;Wang Z;Wu L;Xu S;Wang J;Jiang S;Zhou X;Hoffman AR;Hu X;Hu J;Li T
通讯作者：
Li T
DOI：
10.1016/j.tig.2016.10.002
发表时间：
2016-12
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Chédin F
通讯作者：
Chédin F
影响因子：
16.6
作者：
Bolukbasi MF;Liu P;Luk K;Kwok SF;Gupta A;Amrani N;Sontheimer EJ;Zhu LJ;Wolfe SA
通讯作者：
Wolfe SA
影响因子：
16.6
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
通讯作者：
Fuks F
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B