NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment.
NuRD suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment.
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DOI：
10.1016/j.stem.2012.02.020
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发表时间：
2012-05-04
期刊：
影响因子：
23.9
通讯作者：
Hendrich, Brian
中科院分区：
文献类型：
--
作者：
Reynolds, Nicola;Latos, Paulina;Hynes-Allen, Antony;Loos, Remco;Leaford, Donna;O'Shaughnessy, Aoife;Mosaku, Olukunbi;Signolet, Jason;Brennecke, Philip;Kalkan, Tuezer;Costello, Ita;Humphreys, Peter;Mansfield, William;Nakagawa, Kentaro;Strouboulis, John;Behrens, Axel;Bertone, Paul;Hendrich, Brian
胚胎干细胞（ESC）群体内的转录异质性已被认为是一种机制，通过这种机制，看似同质的细胞群体可以启动分化为一系列不同的细胞类型。染色质重塑蛋白已被证明控制酵母中的转录变异性，并且对哺乳动物ESC谱系定型很重要。在这里，我们表明，核小体重塑和脱乙酰化（NuRD）复合物，这是所需的ESC谱系承诺，调节转录异质性和动态范围的一组多能性基因在ESC中。在自我更新条件下，NuRD对这些基因的影响通过自我更新因子的相反作用来平衡。在失去自我更新因子后，NuRD的作用足以沉默这些多能性基因的转录，允许细胞退出自我更新。我们认为NuRD对转录水平的调节是维持多能细胞分化反应的关键。NuRD直接调节多能性基因的转录NuRD的抑制活性是ESC分化所必需的NuRD介导ESC群体中的转录异质性转录水平由平衡的激活和沉默决定
Transcriptional heterogeneity within embryonic stem cell (ESC) populations has been suggested as a mechanism by which a seemingly homogeneous cell population can initiate differentiation into an array of different cell types. Chromatin remodeling proteins have been shown to control transcriptional variability in yeast and to be important for mammalian ESC lineage commitment. Here we show that the Nucleosome Remodeling and Deacetylation (NuRD) complex, which is required for ESC lineage commitment, modulates both transcriptional heterogeneity and the dynamic range of a set of pluripotency genes in ESCs. In self-renewing conditions, the influence of NuRD at these genes is balanced by the opposing action of self-renewal factors. Upon loss of self-renewal factors, the action of NuRD is sufficient to silence transcription of these pluripotency genes, allowing cells to exit self-renewal. We propose that modulation of transcription levels by NuRD is key to maintaining the differentiation responsiveness of pluripotent cells. ► NuRD directly regulates the transcription of pluripotency genes ► The repressive activity of NuRD is required for ESC differentiation ► NuRD mediates transcriptional heterogeneity in ESC populations ► Transcription levels are determined by balanced activation and silencing
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影响因子：
2.4
作者：
Latos PA;Helliwell C;Mosaku O;Dudzinska DA;Stubbs B;Berdasco M;Esteller M;Hendrich B
通讯作者：
Hendrich B
影响因子：
20.3
作者：
Li, Y;McClintick, J;Chan, RJ
通讯作者：
Chan, RJ
影响因子：
23.9
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
通讯作者：
Surani MA
影响因子：
11.8
作者：
Guo, Guoji;Huss, Mikael;Robson, Paul
通讯作者：
Robson, Paul
DOI：
10.1089/clo.2004.6.386
发表时间：
2004-12-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Chambers, I
通讯作者：
Chambers, I