Pluripotency exit is guided by the Peln1-mediated disruption of intrachromosomal architecture.
Pluripotency exit is guided by the Peln1-mediated disruption of intrachromosomal architecture.
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多能性退出是由 Peln1 介导的染色体内结构破坏引导的
DOI：
10.1083/jcb.202009134
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发表时间：
2022-04-04
期刊：
影响因子：
--
通讯作者：
Hu JF
中科院分区：
文献类型：
--
作者：
Wang Y;Jia L;Wang C;Du Z;Zhang S;Zhou L;Wen X;Li H;Chen H;Nie Y;Li D;Liu S;Figueroa DS;Ay F;Xu W;Zhang S;Li W;Cui J;Hoffman AR;Guo H;Hu JF
Wang等人。确认Peln1是一个关键的染色质InncRNA，它通过反式调节Oct4启动子和维持多能性所需的染色体内环来控制干细胞的多能性退出。导致干细胞退出多能性的分子电路在很大程度上仍未确定。通过染色质RNA原位逆转录测序，我们确定Peln1是干细胞主转录因子基因Oct4启动子复合体中的一个新的染色质RNA组分。在体细胞重编程过程中，Peln1与多能性状态呈负相关。Peln1的过表达导致E14细胞退出多能性，而Peln1的下调诱导了强劲的重新编程。机制上，我们发现Peln1与Oct4启动子相互作用，并招募DNA甲基转移酶DNMT3A。通过重新改变Oct4启动子的表观类型，Peln1拆除了维持多能性所需的染色体内环。利用RNA逆转录相关的TRAP测序，我们发现Peln1针对与干细胞自我更新相关的多个途径基因。这些发现表明，Peln1可以作为一种新的表观遗传学参与者，并使用一种反式机制来诱导干细胞退出多能性状态。
Wang et al. identify Peln1 as a key chromatin lncRNA that controls the pluripotency exit in stem cells by trans regulating the Oct4 promoter and intrachromosomal looping required for the maintenance of pluripotency. The molecular circuitry that causes stem cells to exit from pluripotency remains largely uncharacterized. Using chromatin RNA in situ reverse transcription sequencing, we identified Peln1 as a novel chromatin RNA component in the promoter complex of Oct4, a stem cell master transcription factor gene. Peln1 was negatively associated with pluripotent status during somatic reprogramming. Peln1 overexpression caused E14 cells to exit from pluripotency, while Peln1 downregulation induced robust reprogramming. Mechanistically, we discovered that Peln1 interacted with the Oct4 promoter and recruited the DNA methyltransferase DNMT3A. By de novo altering the epigenotype in the Oct4 promoter, Peln1 dismantled the intrachromosomal loop that is required for the maintenance of pluripotency. Using RNA reverse transcription-associated trap sequencing, we showed that Peln1 targets multiple pathway genes that are associated with stem cell self-renewal. These findings demonstrate that Peln1 can act as a new epigenetic player and use a trans mechanism to induce an exit from the pluripotent state in stem cells.
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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
影响因子：
16.6
作者：
Morgan SL;Mariano NC;Bermudez A;Arruda NL;Wu F;Luo Y;Shankar G;Jia L;Chen H;Hu JF;Hoffman AR;Huang CC;Pitteri SJ;Wang KC
通讯作者：
Wang KC
DOI：
10.1098/rstb.2013.0540
发表时间：
2014-12-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Kalkan T;Smith A
通讯作者：
Smith A
影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
5.8
作者：
He, Sha;Zhang, Hai;Zhu, Hao
通讯作者：
Zhu, Hao