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本帖最后由 qianqianlaile 于 2011-4-14 19:21 编辑
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1 B$ h- ]' p& L" hWdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network
/ \7 w* T$ g. A, Q" C8 ?Cell, 07 April 2011+ m& a& S8 l7 Y" R# U' ^5 v% v
Copyright 2011 Elsevier Inc. All rights reserved.
$ X; ]2 Y( P7 H+ a% {, k, o10.1016/j.cell.2011.03.003
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8 D0 }8 P* z0 d6 W9 EAuthors V8 I5 {& E: d. B+ f3 y. P( W R
Yen-Sin Ang , Su-Yi Tsai, Dung-Fang Lee, Jonathan Monk, Jie Su, Kajan Ratnakumar, Junjun Ding, Yongchao Ge, Henia Darr, Betty Chang, Jianlong Wang, Michael Rendl, Emily Bernstein, Christoph Schaniel, Ihor R. Lemischka See Affiliations- |! u' w6 }0 {
Highlights
& @1 u' P+ s: f0 C- P: i( o• Wdr5 is enriched in ES/iPS cells and is required for ES cell self-renewal & w8 Z: n, q) A8 U9 Q( ]
• Wdr5-Oct4 interaction links core transcriptional network with epigenetic machinery & I7 E3 A: j0 O" {
• Trithorax and core transcriptional network cooperate in transcriptional activation
! z& |/ h0 J% i$ K; j. ~1 q• Wdr5 is required during the initial phases of somatic cell reprogramming2 Q" L/ {: w9 T& {* ` s3 T
Summary
; G& k/ b& P$ q% A( C$ T- J# y) f& [The embryonic stem (ES) cell transcriptional and chromatin-modifying networks are critical for self-renewal maintenance. However, it remains unclear whether these networks functionally interact and, if so, what factors mediate such interactions. Here, we show that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a regulator of ES cell self-renewal. We demonstrate that Wdr5, an effector of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. Genome-wide protein localization and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. The Oct4-Sox2-Nanog circuitry and trxG cooperate in activating transcription of key self-renewal regulators, and furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. We propose an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming.
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" ^, x+ z1 m9 Z1 E; kWdr5通过胚胎干细胞核转录网络介导自我更新和改编 5 J- U9 g5 Z( h' v& s J, ~5 G/ N
细胞杂志 2011-4-7( x7 \2 c2 g% c0 B' P- s* ^+ r! J
版权 2011 爱思唯尔公司拥有所有权利
. x- W0 `1 P: d+ @( H8 R- Q10.1016/j.cell.2011.03.003
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作者
3 D8 K5 E2 h# L- a. [% @/ MYen-Sin Ang , Su-Yi Tsai, Dung-Fang Lee, Jonathan Monk, Jie Su, Kajan Ratnakumar, Junjun Ding, Yongchao Ge, Henia Darr, Betty Chang, Jianlong Wang, Michael Rendl, Emily Bernstein, Christoph Schaniel, Ihor R. Lemischka See Affiliations! Q; a" u8 f+ V* f% `1 W8 I
本研究内容( Q0 k" ~0 ?2 y! T( w0 {
• 胚胎干细胞/诱导多能干细胞中富含Wdr5并且胚胎干细胞自我更新需要Wdr5参与
5 K! D& w3 X: h4 F• Wdr5-Oct4相互作用联系核转录网络和后生机制1 G9 e1 Q; A& ~: f g. `
• Trithorax和核转录网络在转录激活中有协同作用
( c0 P! G# K& b& x8 j9 {! X• 体细胞改编初始期间有Wdr5参与
1 Z% e- a" Z+ H摘要- @9 C3 u4 P8 g, X& U
胚胎干细胞(ES)的转录和染色质修复网是细胞自我更新必需的。然而这些网络是否相互作用以及介导这些可能存在的作用的因子都还不清楚。我们的研究显示与细胞的未分化状态正相关的哺乳动物 Trithorax (trxG) 复合物的核心成员之一的WD重复域5 (Wdr5)是胚胎干细胞自我更新的一个调节物。我们的研究说明H3K4 methylation的一个“受动器”即 Wdr5与多能转录因子Oct4相互作用。全基因组蛋白定位和transcriptome分析显示Oct4 和Wdr5之间有重复基因调节功能。Oct4-Sox2-Nanog circuitry和trxG 在激活关键自我更新调节子转录中有协同作用，此外有效形成诱导多能干细胞(iPS)需要Wdr5表达。我们推断出一个select trxG 成员介导的维持胚胎干细胞自我更新和体细胞改编的转录和epigenetic控制的完整模型。& u: F. [3 e2 F0 U; I3 }: K0 Y" M2 z* J
- L2 y7 k5 }% D不是我的专业领域，很多专业术语都不知道，还望前辈们多多指教 |
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发表于 2011-4-14 19:17
