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SWI/SNF chromatin remodeling controls Notch‐responsive enhancer accessibility

机译:SWI / SNF染色质重塑控制缺口响应增强子的可及性

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摘要

Notch signaling plays a key role in many cell fate decisions during development by directing different gene expression programs via the transcription factor , known as Su(H) in . Which target genes are responsive to Notch signaling is influenced by the chromatin state of enhancers, yet how this is regulated is not fully known. Detecting a specific increase in the histone variant H3.3 in response to Notch signaling, we tested which chromatin remodelers or histone chaperones are required for the changes in enhancer accessibility to Su(H) binding. We show a crucial role for the Brahma / chromatin remodeling complex, including the actin‐related 55 subunit, in conferring enhancer accessibility and enabling the transcriptional response to Notch activity. The Notch‐responsive regions have high levels of nucleosome turnover which depend on the Brahma complex, increase in magnitude with Notch signaling, and primarily involve histone H3.3. Together these results highlight the importance of / ‐mediated nucleosome turnover in rendering enhancers responsive to Notch.
机译:Notch信号在发育过程中的许多细胞命运决策中起着关键作用,通过转录因子(在Su4中称为Su(H))指导不同的基因表达程序。哪些靶基因对Notch信号有反应受增强子的染色质状态影响,但如何调节尚不清楚。检测到响应Notch信号的组蛋白变体H3.3的特定增加,我们测试了对于Su(H)结合的增强子可及性的变化需要哪些染色质重塑剂或组蛋白伴侣。我们展示了梵天/染色质重塑复合体(包括肌动蛋白相关的55个亚基)在赋予增强子可及性和实现对Notch活性的转录反应中的关键作用。 Notch反应区具有高水平的核小体周转率,这取决于Brahma复合体,随着Notch信号传导而增加,并且主要涉及组蛋白H3.3。这些结果共同强调了/介导的核小体更新在增强Notch应答中的重要性。

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