The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells
The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells
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核小体重塑和脱乙酰化复合物协调多能细胞中谱系定型的转录反应
DOI：
10.1101/2023.02.09.527610
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Montibus B
中科院分区：
文献类型：
--
作者：
Montibus B
当细胞退出多能性状态并开始致力于特定的谱系时，它们必须激活适合该谱系的基因，同时沉默与多能性相关的基因，并防止激活不适合谱系的基因。核小体重塑和去乙酰化(NuRD)复合体对于多能细胞成功地进行谱系承诺是必不可少的。NuRD在调控序列上控制核小体密度，以促进转录反应，也已被证明可以防止未分化的多能细胞中的非程序性转录(转录噪声)。这些活动如何结合以确保细胞参与适合于成功的谱系承诺的基因表达程序尚未确定。在这里，我们展示了NuRD并不需要沉默所有的基因。相反，它限制了在退出多能性状态时准备激活的基因的表达，但在自我更新的条件下将它们保持在转录允许的状态，这有助于它们在退出天真多能性时随后的激活。我们进一步表明，NuRD协调基因表达的变化，这是为了维持不同稳定状态之间的屏障。因此，NuRD介导的染色质重塑具有多种功能，包括减少转录噪声、启动基因激活以及协调转录反应以促进谱系承诺。
As cells exit the pluripotent state and begin to commit to a specific lineage they must activate genes appropriate for that lineage while silencing genes associated with pluripotency and preventing activation of lineage-inappropriate genes. The Nucleosome Remodelling and Deacetylation (NuRD) complex is essential for pluripotent cells to successfully undergo lineage commitment. NuRD controls nucleosome density at regulatory sequences to facilitate transcriptional responses, and also has been shown to prevent unscheduled transcription (transcriptional noise) in undifferentiated pluripotent cells. How these activities combine to ensure cells engage a gene expression program suitable for successful lineage commitment has not been determined. Here, we show that NuRD is not required to silence all genes. Rather, it restricts expression of genes primed for activation upon exit from the pluripotent state, but maintains them in a transcriptionally permissive state in self-renewing conditions, which facilitates their subsequent activation upon exit from naïve pluripotency. We further show that NuRD coordinates gene expression changes, which acts to maintain a barrier between different stable states. Thus NuRD-mediated chromatin remodelling serves multiple functions, including reducing transcriptional noise, priming genes for activation and coordinating the transcriptional response to facilitate lineage commitment.
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影响因子：
4.5
作者：
Yang SH;Kalkan T;Morrisroe C;Smith A;Sharrocks AD
通讯作者：
Sharrocks AD
DOI：
10.1126/science.1248882
发表时间：
2014-06-06
期刊：
Science (New York, N.Y.)
影响因子：
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DOI：
10.1111/febs.13132
发表时间：
2015-05
期刊：
The FEBS journal
影响因子：
--
作者：
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通讯作者：
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影响因子：
14.9
作者：
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