Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression.
Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression.
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YAP的相位分离重新组织了基因组拓扑，以进行长期YAP靶基因表达。
DOI：
10.1038/s41556-019-0433-z
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发表时间：
2019-12
影响因子：
21.3
通讯作者：
Lippincott-Schwartz J
中科院分区：
文献类型：
--
作者：
Cai D;Feliciano D;Dong P;Flores E;Gruebele M;Porat-Shliom N;Sukenik S;Liu Z;Lippincott-Schwartz J
是相关蛋白（雅普）是一种转录辅激活因子，通过与靶基因激活的一组选择性增强子结合来调节细胞增殖和存活。雅普如何协调这些转录反应尚不清楚。在这里，我们证明了雅普在核中形成液体状凝聚物。雅普在高渗胁迫的几秒钟内形成，浓缩了区室化的雅普的转录因子TEAD 1和其他YAP相关的共激活因子，包括TAZ，随后诱导YAP特异性增殖基因的转录。使用具有光活化定位显微镜的转座酶可吸收染色质测定（ATAC-PALM）的超分辨率成像显示，雅普核浓缩物是富集在组织为超级增强子的可接近的染色质结构域中的区域。最初缺乏RNA聚合酶II（RNAPII），可接近的染色质结构域后来获得RNAPII，转录RNA。去除雅普的内在无序的转录激活结构域（KAP）阻止了雅普缩合物的形成并减少了下游雅普信号传导。因此，在雅普重编程过程中基因组组织和基因活化的动态变化由液-液相分离介导。
Yes-associated Protein (YAP) is a transcriptional co-activator that regulates cell proliferation and survival by binding to a select set of enhancers for target gene activation. How YAP coordinates these transcriptional responses is unknown. Here, we demonstrate that YAP forms liquid-like condensates in the nucleus. Formed within seconds of hyperosmotic stress, YAP condensates compartmentalized YAP’s transcription factor TEAD1 and other YAP-related co-activators, including TAZ, and subsequently induced transcription of YAP-specific proliferation genes. Super-resolution imaging using Assay for Transposase Accessible Chromatin with photoactivated localization microscopy (ATAC-PALM) revealed that YAP nuclear condensates were areas enriched in accessible chromatin domains organized as super-enhancers. Initially devoid of RNA Polymerase II (RNAPII), the accessible chromatin domains later acquired RNAPII, transcribing RNA. Removal of YAP’s intrinsically-disordered transcription activation domain (TAD) prevented YAP condensate formation and diminished downstream YAP signaling. Thus, dynamic changes in genome organization and gene activation during YAP reprogramming is mediated by liquid-liquid phase separation.
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影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
158.5
作者：
JAMISON, RL;MAFFLY, RH
通讯作者：
MAFFLY, RH
影响因子：
64.8
作者：
Larson AG;Elnatan D;Keenen MM;Trnka MJ;Johnston JB;Burlingame AL;Agard DA;Redding S;Narlikar GJ
通讯作者：
Narlikar GJ
影响因子：
64.5
作者：
Boija A;Klein IA;Sabari BR;Dall'Agnese A;Coffey EL;Zamudio AV;Li CH;Shrinivas K;Manteiga JC;Hannett NM;Abraham BJ;Afeyan LK;Guo YE;Rimel JK;Fant CB;Schuijers J;Lee TI;Taatjes DJ;Young RA
通讯作者：
Young RA