LncPRESS1 Is a p53-Regulated LncRNA that Safeguards Pluripotency by Disrupting SIRT6-Mediated De-acetylation of Histone H3K56.
LncPRESS1 Is a p53-Regulated LncRNA that Safeguards Pluripotency by Disrupting SIRT6-Mediated De-acetylation of Histone H3K56.
复制标题
DOI：
10.1016/j.molcel.2016.10.039
复制
发表时间：
2016-12-01
期刊：
影响因子：
16
通讯作者：
Barton MC
中科院分区：
文献类型：
--
作者：
Jain AK;Xi Y;McCarthy R;Allton K;Akdemir KC;Patel LR;Aronow B;Lin C;Li W;Yang L;Barton MC
最近的证据表明，lncRNA在许多功能中起着不可或缺的调节作用，包括确定细胞的身份。我们确定了在经历分化的人胚胎干细胞（hESC）中组蛋白翻译后修饰和p53结合的全局表达（RNA-seq）和全基因组谱（ChIP-seq），以定义40个lncRNA的高置信度集，这些lncRNA是p53转录靶点。我们重点研究了在多能hESC中高度表达并在分化过程中被p53抑制的lncRNA，以鉴定lncPRES 1是一种p53调节的转录本，它与核心多能性因子一起维持hESC多能性。对缺失lncRNA 1的hESC的RNA-seq显示lncRNA 1控制促进多能性的基因网络。此外，我们发现lnceptin 1与SIRT 6物理相互作用并阻止SIRT 6染色质定位，这在多能性基因的启动子处维持高水平的组蛋白H3 K56和H3 K9乙酰化。总之，我们描述了一种p53调节的多能性特异性lncRNA，通过破坏SIRT 6活性来保护hESC状态。
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors. RNA-seq of hESCs depleted of lncPRESS1 revealed that lncPRESS1 controls a gene network that promotes pluripotency. Further, we found that lncPRESS1 physically interacts with SIRT6 and prevents SIRT6 chromatin localization, which maintains high levels of histone H3K56 and H3K9 acetylation at promoters of pluripotency genes. In summary, we describe a p53-regulated, pluripotency-specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity.
登录
查看更多内容
影响因子：
13.8
作者：
Kugel, Site;Mostoslavsky, Raul
通讯作者：
Mostoslavsky, Raul
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：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
JPX RNA通过驱逐CTCF激活XIST。
影响因子：
64.5
作者：
Sun S;Del Rosario BC;Szanto A;Ogawa Y;Jeon Y;Lee JT
通讯作者：
Lee JT
RNA在意外的地方：长的非编码RNA在不同的细胞环境中起作用。
DOI：
10.1038/nrm3679
发表时间：
2013-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Geisler S;Coller J
通讯作者：
Coller J