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引用次数: 0
摘要
组蛋白变体 H2A.Z 存在于启动子中并调节转录。依赖 ATP 的染色质重塑者 SRCAP 复合物(SRCAP-C)能促进 H2A.Z-H2B 二聚体取代标准组蛋白 H2A-H2B 二聚体。在这里,我们以接近原子分辨率测定了人类 SRCAP-C 与含 H2A 核小体结合的结构。SRCAP亚基整合了一个6亚基肌动蛋白相关蛋白(ARP)模块和一个含ATP酶的马达模块。与 ATPase 相关的 ARP 模块沿 DNA 环绕核小体的一半,可抑制 DNA 的净移位,这是 SRCAP-C 的独特之处。马达模块在无核苷酸、ADP结合和ADP-BeFx结合状态下采用不同的核小体结合模式,表明ATP酶驱动的运动通过解开入口DNA来破坏H2A-H2B的稳定性,并通过ZNHIT1亚基将H2A-H2B拉出核小体。结构引导的染色质免疫沉淀测序分析证实,H2A接触ZNHIT1在维持H2A.Z在基因组上的占有率方面是必需的。我们的研究从结构上揭示了 SRCAP-C 介导的 H2A-H2A.Z 交换机制。
Structural insights into histone exchange by human SRCAP complex.
Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A-H2B dimer with H2A.Z-H2B dimer. Here, we determined structures of human SRCAP-C bound to H2A-containing nucleosome at near-atomic resolution. The SRCAP subunit integrates a 6-subunit actin-related protein (ARP) module and an ATPase-containing motor module. The ATPase-associated ARP module encircles half of the nucleosome along the DNA and may restrain net DNA translocation, a unique feature of SRCAP-C. The motor module adopts distinct nucleosome binding modes in the apo (nucleotide-free), ADP-bound, and ADP-BeFx-bound states, suggesting that ATPase-driven movement destabilizes H2A-H2B by unwrapping the entry DNA and pulls H2A-H2B out of nucleosome through the ZNHIT1 subunit. Structure-guided chromatin immunoprecipitation sequencing analysis confirmed the requirement of H2A-contacting ZNHIT1 in maintaining H2A.Z occupancy on the genome. Our study provides structural insights into the mechanism of H2A-H2A.Z exchange mediated by SRCAP-C.
Cell DiscoveryBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍:
Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research.
Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals.
In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.