ΔNp63 is a pioneer factor that binds inaccessible chromatin and elicits chromatin remodeling.
ΔNp63 is a pioneer factor that binds inaccessible chromatin and elicits chromatin remodeling.
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ΔNp63是结合不可接近的染色质和弹性染色质重塑的先锋因子。
DOI：
10.1186/s13072-021-00394-8
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发表时间：
2021-04-17
影响因子：
3.9
通讯作者：
Buck MJ
中科院分区：
文献类型：
--
作者：
Yu X;Singh PK;Tabrejee S;Sinha S;Buck MJ
ΔNp63是一个主要的转录调节因子，在表皮发育和其他细胞过程中起关键作用。最近的研究表明ΔNp63作为一种先锋因子，可以在不可接近的染色质中靶向其结合位点并诱导染色质重塑。为了检查ΔNp63是否可以与不可接近的染色质结合，并确定是否需要特定的组蛋白修饰来结合，我们在两个p63-naïve细胞系中诱导了ΔNp63的表达。然后通过ChIP-seq检测ΔNp63结合，并在结合前后检测ΔNp63目标位点的染色质。使用竞争性核小体结合试验进一步分析，以确定ΔNp63如何直接与核小体相互作用。我们的研究结果表明，在ΔNp63结合之前，目标位点缺乏组蛋白修饰，这表明ΔNp63能够结合未修饰的染色质。此外，大多数异位ΔNp63表达结合的位点处于不可访问状态。一旦结合，ΔNp63诱导组蛋白乙酰化和核小体在其结合位点的重新定位。通过竞争核小体结合实验进一步分析发现ΔNp63可以直接结合核小体边缘，在核小体二联体的50 bp内发生显著的结合抑制。总的来说，我们的研究结果表明ΔNp63是一个先驱因子，它结合核小体边缘在不可接近和未修饰的染色质位点，并诱导组蛋白乙酰化和核小体重定位。在线版本包含补充材料，可在10.1186/s13072-021-00394-8获得。
ΔNp63 is a master transcriptional regulator playing critical roles in epidermal development and other cellular processes. Recent studies suggest that ΔNp63 functions as a pioneer factor that can target its binding sites within inaccessible chromatin and induce chromatin remodeling. In order to examine if ΔNp63 can bind to inaccessible chromatin and to determine if specific histone modifications are required for binding, we induced ΔNp63 expression in two p63-naïve cell lines. ΔNp63 binding was then examined by ChIP-seq and the chromatin at ΔNp63 targets sites was examined before and after binding. Further analysis with competitive nucleosome binding assays was used to determine how ΔNp63 directly interacts with nucleosomes. Our results show that before ΔNp63 binding, targeted sites lack histone modifications, indicating ΔNp63’s capability to bind at unmodified chromatin. Moreover, the majority of the sites that are bound by ectopic ΔNp63 expression exist in an inaccessible state. Once bound, ΔNp63 induces acetylation of the histone and the repositioning of nucleosomes at its binding sites. Further analysis with competitive nucleosome binding assays reveal that ΔNp63 can bind directly to nucleosome edges with significant binding inhibition occurring within 50 bp of the nucleosome dyad. Overall, our results demonstrate that ΔNp63 is a pioneer factor that binds nucleosome edges at inaccessible and unmodified chromatin sites and induces histone acetylation and nucleosome repositioning. The online version contains supplementary material available at 10.1186/s13072-021-00394-8.
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