Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states.
Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states.
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DOI：
10.1038/s41467-021-22201-4
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发表时间：
2021-04-07
影响因子：
16.6
通讯作者：
Rugg-Gunn PJ
中科院分区：
文献类型：
--
作者：
Chovanec P;Collier AJ;Krueger C;Várnai C;Semprich CI;Schoenfelder S;Corcoran AE;Rugg-Gunn PJ
从幼稚到引发的多能性的转变伴随着转录和表观遗传程序的广泛重组。然而，转录增强子和三维染色质组织在协调这些发展计划中的作用仍然不完全清楚。在这里，我们生成了一个高分辨率的基因调控相互作用，染色质配置文件和转录因子占用在幼稚和启动人类多能干细胞的图谱，并开发了一个网络图的方法来检查在多个空间尺度的图谱。我们发现了高度连接的启动子枢纽，这些枢纽在多能状态之间的相互作用频率和转录共调控方面发生了重大变化。小的枢纽经常合并，在启动细胞中形成更大的网络，通常通过新形成的Polycomb相关相互作用连接。我们确定了增强子活性和相互作用的广泛状态特异性差异，这与OCT 4，SOX 2和NANOG结合和靶基因表达的广泛重新配置相对应。这些发现为基于染色质的人类多能状态的基因调控提供了多层次的见解。转录增强子和3D染色质组织在协调从幼稚到引发多能性的转变中的作用仍然知之甚少。在这里，作者生成了一个高分辨率的基因调控相互作用图谱，染色质谱和转录因子在幼稚和启动的人类多能干细胞中的占有率，以提供对这些发育过程的见解。
The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells, and develop a network-graph approach to examine the atlas at multiple spatial scales. We uncover highly connected promoter hubs that change substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merge to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. We identify widespread state-specific differences in enhancer activity and interactivity that correspond with an extensive reconfiguration of OCT4, SOX2 and NANOG binding and target gene expression. These findings provide multilayered insights into the chromatin-based gene regulatory control of human pluripotent states. The role of transcriptional enhancers and 3D chromatin organisation in coordinating the transition from naive to primed pluripotency remains poorly understood. Here the authors generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells to provide insights into these developmental processes.
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DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
7
作者：
Beagan JA;Duong MT;Titus KR;Zhou L;Cao Z;Ma J;Lachanski CV;Gillis DR;Phillips-Cremins JE
通讯作者：
Phillips-Cremins JE
影响因子：
4.6
作者：
Chen, Weisheng V.;Maniatis, Tom
通讯作者：
Maniatis, Tom
影响因子：
64.5
作者：
Bonev B;Mendelson Cohen N;Szabo Q;Fritsch L;Papadopoulos GL;Lubling Y;Xu X;Lv X;Hugnot JP;Tanay A;Cavalli G
通讯作者：
Cavalli G
影响因子：
64.8
作者：
Beagrie RA;Scialdone A;Schueler M;Kraemer DC;Chotalia M;Xie SQ;Barbieri M;de Santiago I;Lavitas LM;Branco MR;Fraser J;Dostie J;Game L;Dillon N;Edwards PA;Nicodemi M;Pombo A
通讯作者：
Pombo A