Structure-function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2.
Structure-function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2.
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DOI：
10.1101/gad.261115.115
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发表时间：
2015-06-15
影响因子：
10.5
通讯作者：
Patel DJ
中科院分区：
文献类型：
--
作者：
Chen S;Rufiange A;Huang H;Rajashankar KR;Nourani A;Patel DJ
在这项研究中，Patel 及其同事确定了与 H3/H4 四聚体结合的 hSpt2C 组蛋白伴侣的保守 C 末端的晶体结构。结果表明Spt2与H3/H4四聚体的外围相互作用并促进其回收。细胞使用组蛋白伴侣等特定机制来消除核小体对转录聚合酶造成的固有障碍。目前的模型假设核小体可以被短暂破坏以适应 RNA 聚合酶的通过，并且组蛋白 H3 和 H4 拥有自己的伴侣，致力于核小体的恢复。在这里，我们确定了与 H3/H4 四聚体结合的人 Ty 插入抑制因子 2 (hSpt2C) 分子伴侣的保守 C 末端的晶体结构。结构研究表明，hSpt2C 与 H3/H4 四聚体的外围结合，模仿核小体结合 DNA 的轨迹。这些结构研究得到了对突变体的体外结合和体内功能研究的补充，这些突变体破坏了涉及 Spt2C 上两个酸性斑块和疏水残基的关键分子间接触。我们表明，人类和酵母 Spt2C 与 H3/H4 四聚体之间的接触是抑制 H3/H4 交换所必需的，这通过 H3K56ac 和新的 H3 沉积来测量。这些相互作用对于抑制编码区内的虚假转录也至关重要。总之，我们的数据表明 Spt2 与 H3/H4 四聚体的外围相互作用，并在 RNA 聚合酶之后促进其回收。
In this study, Patel and colleagues determined the crystal structure of the conserved C terminus of the hSpt2C histone chaperone bound to an H3/H4 tetramer. The results suggest that Spt2 interacts with the periphery of the H3/H4 tetramer and promotes its recycling. Cells use specific mechanisms such as histone chaperones to abrogate the inherent barrier that the nucleosome poses to transcribing polymerases. The current model postulates that nucleosomes can be transiently disrupted to accommodate passage of RNA polymerases and that histones H3 and H4 possess their own chaperones dedicated to the recovery of nucleosomes. Here, we determined the crystal structure of the conserved C terminus of human Suppressors of Ty insertions 2 (hSpt2C) chaperone bound to an H3/H4 tetramer. The structural studies demonstrate that hSpt2C is bound to the periphery of the H3/H4 tetramer, mimicking the trajectory of nucleosomal-bound DNA. These structural studies have been complemented with in vitro binding and in vivo functional studies on mutants that disrupt key intermolecular contacts involving two acidic patches and hydrophobic residues on Spt2C. We show that contacts between both human and yeast Spt2C with the H3/H4 tetramer are required for the suppression of H3/H4 exchange as measured by H3K56ac and new H3 deposition. These interactions are also crucial for the inhibition of spurious transcription from within coding regions. Together, our data indicate that Spt2 interacts with the periphery of the H3/H4 tetramer and promotes its recycling in the wake of RNA polymerase.
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DOI：
10.1083/jcb.153.7.1341
发表时间：
2001-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kimura H;Cook PR
通讯作者：
Cook PR
影响因子：
64.8
作者：
Natsume, Ryo;Eitoku, Masamitsu;Senda, Toshiya
通讯作者：
Senda, Toshiya
影响因子：
10.5
作者：
KRUGER, W;PETERSON, CL;HERSKOWITZ, I
通讯作者：
HERSKOWITZ, I
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
56.9
作者：
Dion, Michael F.;Kaplan, Tommy;Rando, Oliver J.
通讯作者：
Rando, Oliver J.