Genome information processing by the INO80 chromatin remodeler positions nucleosomes.
Genome information processing by the INO80 chromatin remodeler positions nucleosomes.
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DOI：
10.1038/s41467-021-23016-z
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发表时间：
2021-05-28
影响因子：
16.6
通讯作者：
Eustermann S
中科院分区：
文献类型：
--
作者：
Oberbeckmann E;Krietenstein N;Niebauer V;Wang Y;Schall K;Moldt M;Straub T;Rohs R;Hopfner KP;Korber P;Eustermann S
ATP依赖的染色质重塑组织核小体在真核生物基因组中的基本分子决定因素仍然很难理解。在这里，染色质重构生理，全基因组模板揭示了重塑如何读取和翻译基因组信息到核小体的位置。使用酵母基因组和多亚基INO 80重塑作为范例，我们确定DNA形状/力学编码的签名图案作为足够的核小体定位和不同于已知的DNA序列偏好的组蛋白。INO 80通过其核心和Arp 8模块之间的变构相互作用来处理这些信息，该模块探测核小体和接头DNA的机械性质。在启动子处，INO 80通过与结合到这些基序的一般调节因子的相互作用，将DNA形状/力学的这种读出与共进化序列基序的读出整合。我们的研究结果建立了一个强大的，但可调节的+1核小体定位的分子机制，更一般地说，重塑作为信息处理中心，使主动组织和变构调节的第一级染色质。DNA序列的偏好或组蛋白的统计定位并没有解释体内核小体组织的基因组模式。在这里，作者将DNA形状/力学确定为与DNA序列特异性屏障的结合位点一起进化的关键元素，以便这些信息通过染色质重塑指导核小体定位。
The fundamental molecular determinants by which ATP-dependent chromatin remodelers organize nucleosomes across eukaryotic genomes remain largely elusive. Here, chromatin reconstitutions on physiological, whole-genome templates reveal how remodelers read and translate genomic information into nucleosome positions. Using the yeast genome and the multi-subunit INO80 remodeler as a paradigm, we identify DNA shape/mechanics encoded signature motifs as sufficient for nucleosome positioning and distinct from known DNA sequence preferences of histones. INO80 processes such information through an allosteric interplay between its core- and Arp8-modules that probes mechanical properties of nucleosomal and linker DNA. At promoters, INO80 integrates this readout of DNA shape/mechanics with a readout of co-evolved sequence motifs via interaction with general regulatory factors bound to these motifs. Our findings establish a molecular mechanism for robust and yet adjustable +1 nucleosome positioning and, more generally, remodelers as information processing hubs that enable active organization and allosteric regulation of the first level of chromatin. DNA sequence preferences or statistical positioning of histones has not explained genomic patterns of nucleosome organisation in vivo. Here, the authors establish DNA shape/mechanics as key elements that have evolved together with binding sites of DNA sequence-specific barriers so that such information directs nucleosome positioning by chromatin remodelers.
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