H2A.Z deposition by the SWR complex is stimulated by polyadenine DNA sequences in nucleosomes.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2025-05-12 eCollection Date: 2025-05-01 DOI:10.1371/journal.pbio.3003059
Cynthia Converso, Leonidas Pierrakeas, Lirong Chan, Shalvi Chowdhury, Emily de Onis, Vyacheslav I Kuznetsov, John M Denu, Ed Luk
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引用次数: 0

Abstract

The variant histone H2A.Z is deposited into nucleosomes immediately downstream of promoters, where it plays a critical role in transcription. The site-specific deposition of H2A.Z is catalyzed by the SWR complex, a conserved chromatin remodeler with affinity for promoter-proximal nucleosome-depleted regions (NDRs) and histone acetylation. By comparing the genomic distribution of H2A.Z in wild-type and SWR-deficient cells, we found that SWR is also responsible for depositing H2A.Z at thousands of non-canonical sites not directly linked to NDRs or histone acetylation. To understand the targeting mechanism of H2A.Z, we presented SWR to a library of canonical nucleosomes isolated from yeast and analyzed the preferred substrates. Our results revealed that SWR preferentially deposited H2A.Z into a subset of endogenous H2A.Z sites, which are overrepresented by polyadenine tracts on the top strands of the DNA duplex at the nucleosomal entry-exit sites. Insertion of polyadenine sequences into recombinant nucleosomes near the outgoing H2A-H2B dimer enhanced SWR's affinity for the nucleosomal substrate and increased its H2A.Z insertion activity. These findings suggest that the genome encodes sequence-based information that facilitates remodeler-mediated targeting of H2A.Z.

H2A。核小体中的多腺嘌呤DNA序列刺激SWR复合物的Z沉积。
变异组蛋白H2A。Z在启动子下游的核小体中沉积,在那里它在转录中起着关键作用。H2A的位点特异性沉积。Z由SWR复合物催化,SWR复合物是一种保守的染色质重塑剂,具有启动子-近端核小体缺失区(NDRs)和组蛋白乙酰化的亲和力。通过比较H2A的基因组分布。在野生型和SWR缺陷细胞中,我们发现SWR也负责沉积H2A。Z在数千个非规范位点上,与ndr或组蛋白乙酰化没有直接联系。了解H2A的靶向机制。最后,我们对从酵母中分离的典型核小体文库进行了SWR,并分析了首选底物。结果表明,SWR优先沉积H2A。Z转化为内源性H2A的一个子集。在核小体进出位点上,DNA顶部链上的多聚腺嘌呤束过多地代表了Z位点。将多聚腺嘌呤序列插入到外发H2A- h2b二聚体附近的重组核小体中,增强了SWR对核小体底物的亲和力,并增加了其H2A。Z插入活动。这些发现表明,基因组编码基于序列的信息,促进了重塑蛋白介导的h2a - z靶向。
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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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