Partitioned usage of chromatin remodelers by nucleosome-displacing factors.
Partitioned usage of chromatin remodelers by nucleosome-displacing factors.
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DOI：
10.1016/j.celrep.2022.111250
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发表时间：
2022-08-23
期刊：
影响因子：
8.8
通讯作者：
Bai, Lu
中科院分区：
文献类型：
--
作者：
Chen, Hengye;Kharerin, Hungyo;Dhasarathy, Archana;Kladde, Michael;Bai, Lu
酵母中的核小体置换因子（NDF）类似于高等真核生物中的先驱因子，可以打开封闭的染色质并产生核小体缺失区（NDRs）。酵母中的NDRs也受到ATP依赖性染色质重塑（CR）的影响。然而，NDF和CRs如何在核小体侵入和NDR形成中协调仍不清楚。在这里，我们设计了一个高通量的方法来系统地研究NDF和CR之间的相互作用。通过将集成的合成寡核苷酸文库与基于DNA甲基转移酶的单分子核小体作图相结合，我们测量了CR对单个NDF产生的NDRs的影响。我们发现CRs参与了NDF对核小体的侵袭，并且它们在NDF结合的下游起调节NDR长度的作用。少数CR对某些NDF表现出高度特异性;然而，在大多数情况下，CR以因子非特异性和NDR长度依赖性方式募集。总的来说，我们的研究提供了一个框架，探讨如何NDF和CRs合作，以调节染色质开放。酵母中的染色质可及性受核小体置换因子（NDF）和染色质重塑因子（CR）调节。Chen等人表明，NDF首先侵入核小体，然后招募CR来调节NDR长度。CR的NDF特异性和NDR长度依赖性募集允许NDF对CR的分区使用。
Nucleosome-displacing-factors (NDFs) in yeast, similar to pioneer factors in higher eukaryotes, can open closed chromatin and generate nucleosome-depleted regions (NDRs). NDRs in yeast are also affected by ATP-dependent chromatin remodelers (CRs). However, how NDFs and CRs coordinate in nucleosome invasion and NDR formation is still unclear. Here, we design a high-throughput method to systematically study the interplay between NDFs and CRs. By combining an integrated synthetic oligonucleotide library with DNA methyltransferase-based, single-molecule nucleosome mapping, we measure the impact of CRs on NDRs generated by individual NDFs. We find that CRs are dispensable for nucleosome invasion by NDFs, and they function downstream of NDF binding to modulate the NDR length. A few CRs show high specificity toward certain NDFs; however, in most cases, CRs are recruited in a factor-nonspecific and NDR length-dependent manner. Overall, our study provides a framework to investigate how NDFs and CRs cooperate to regulate chromatin opening. Chromatin accessibility in yeast is regulated by nucleosome-displacing-factors (NDFs) and chromatin remodelers (CRs). Chen et al. show that NDFs first invade into nucleosomes and then recruit CRs to modulate the NDR length. NDF-specific and NDR length-dependent recruitment of CRs allow partitioned usage of CRs by NDFs.
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