Dynamics of Histone H3 Deposition In Vivo Reveal a Nucleosome Gap-Filling Mechanism for H3.3 to Maintain Chromatin Integrity
Dynamics of Histone H3 Deposition In Vivo Reveal a Nucleosome Gap-Filling Mechanism for H3.3 to Maintain Chromatin Integrity
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DOI：
10.1016/j.molcel.2011.12.006
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发表时间：
2011-12-23
期刊：
影响因子：
16
通讯作者：
Almouzni, Genevieve
中科院分区：
文献类型：
--
作者：
Ray-Gallet, Dominique;Woolfe, Adam;Almouzni, Genevieve
建立适当的染色质景观对于基因组功能至关重要。在这里，我们通过涉及 CAF-1 和 HIRA 组蛋白伴侣的特定靶向和沉积动力学来解释 H3 变体分布。通过 CAF-1 损害复制性 H3.1 掺入，可以通过 HIRA 在复制位点替代 H3.3 沉积。相反，H3.3 通过 HIRA 掺入整个细胞周期不能被 H3.1 取代。 ChIP-seq 分析揭示了 HIRA 依赖性 H3.3 积累与转录位点和特定调控元件上的 RNA pol II 之间的相关性，并得到其生化关联的进一步支持。 HIRA 复合物显示出独特的 DNA 结合特性，HIRA 的消耗会增加 DNA 对核酸酶的敏感性。我们提出，HIRA 对裸露 DNA 的保护性核小体间隙填充导致 H3.3 的广泛分布，而 HIRA 与 Pol II 的关联确保了特定位点的局部 H3.3 富集。我们讨论了 H3.3 沉积作为维持染色质完整性的挽救途径的重要性。
Establishment of a proper chromatin landscape is central to genome function. Here, we explain H3 variant distribution by specific targeting and dynamics of deposition involving the CAF-1 and HIRA histone chaperones. Impairing replicative H3.1 incorporation via CAF-1 enables an alternative H3.3 deposition at replication sites via HIRA. Conversely, the H3.3 incorporation throughout the cell cycle via HIRA cannot be replaced by H3.1. ChIP-seq analyses reveal correlation between HIRA-dependent H3.3 accumulation and RNA pol II at transcription sites and specific regulatory elements, further supported by their biochemical association. The HIRA complex shows unique DNA binding properties, and depletion of HIRA increases DNA sensitivity to nucleases. We propose that protective nucleosome gap filling of naked DNA by HIRA leads to a broad distribution of H3.3, and HIRA association with Pol II ensures local H3.3 enrichment at specific sites. We discuss the importance of this H3.3 deposition as a salvage pathway to maintain chromatin integrity.