0 [% Q/ g- v( g; `& ~8 B8 q8 d& ATranscriptional Pause Release Is a Rate-Limiting Step for Somatic Cell Reprogramming ' ~* n. a* B+ }8 N. m+ s/ u5 }' m0 s8 mLongqi Liu14, Yan Xu14, Minghui He14, Meng Zhang, Fenggong Cui, Leina Lu, Mingze Yao, Weihua Tian, Christina Benda, Qiang Zhuang, Zhijian Huang, Wenjuan Li, Xiangchun Li, Ping Zhao, Wenxia Fan, Zhiwei Luo, Yuan Li, Yasong Wu, Andrew P. Hutchins, Dongye Wang, Hung-Fat Tse, Axel Schambach, Jon Frampton, Baoming Qin, Xichen Bao, Hongjie Yao, Biliang Zhang, Hao Sun, Duanqing Pei, Huating Wang, Jun Wang, Miguel A. Esteban! ~' ~: M* L3 G \
a# I& ~9 ?5 K# O3 T2 y , \3 s1 l" v6 s: c- GHighlights - } i8 F- n: I1 J•Pol II is paused at pluripotency genes during reprogramming 0 M9 i. b1 v, ]$ U* i•P-TEFb induces transcriptional elongation at pluripotency genes in reprogramming! Y# d6 B2 }9 `* [9 G0 C
•BRD4 and HEXIM1 have opposite roles in reprogramming+ R7 N: K4 g4 b9 R2 r0 Y! `3 v
•KLF4 helps recruit P-TEFb to pluripotency genes in reprogramming and ESCs; E; w( H; ]& k, a6 C8 X
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Summary 6 [- O" g" c" Y# ^Reactivation of the pluripotency network during somatic cell reprogramming by exogenous transcription factors involves chromatin remodeling and the recruitment of RNA polymerase II (Pol II) to target loci. Here, we report that Pol II is engaged at pluripotency promoters in reprogramming but remains paused and inefficiently released. We also show that bromodomain-containing protein 4 (BRD4) stimulates productive transcriptional elongation of pluripotency genes by dissociating the pause release factor P-TEFb from an inactive complex containing HEXIM1. Consequently, BRD4 overexpression enhances reprogramming efficiency and HEXIM1 suppresses it, whereas Brd4 and Hexim1 knockdown do the opposite. We further demonstrate that the reprogramming factor KLF4 helps recruit P-TEFb to pluripotency promoters. Our work thus provides a mechanism for explaining the reactivation of pluripotency genes in reprogramming and unveils an unanticipated role for KLF4 in transcriptional pause release.9 H. T; n6 D% L! Z
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4楼原文 感谢zm19900508 提供作者: zm19900508 时间: 2014-10-10 09:17
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广州生物医药与健康研究院Miguel组的刘龙奇和许燕博士最新研究发现多能性基因的激活是体细胞重编程的限速步骤。这是首次研究转录延伸在体细胞重编程里的关键作用。作者: thinktank 时间: 2014-10-10 09:32