Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.
Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.
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DOI：
10.1038/s41467-018-05581-y
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发表时间：
2018-08-06
影响因子：
16.6
通讯作者：
Almouzni G
中科院分区：
文献类型：
--
作者：
Ray-Gallet D;Ricketts MD;Sato Y;Gupta K;Boyarchuk E;Senda T;Marmorstein R;Almouzni G
Hira组蛋白伴侣复合体以一种不依赖DNA合成的方式将组蛋白变体H3.3沉积到染色质上。它由HIRA、UBN1和CABIN1三个亚基组成，但该复合体的功能寡聚状态尚未被研究。在这里，我们使用生化和结晶学分析表明，Hira亚基在体外形成一个稳定的同源三聚体，与CABIN1的两个亚基结合。同源三聚体形成缺陷的Hira突变体与CABIN1的相互作用效率较低，在紫外线照射下不会在DNA损伤部位浓缩，也不能挽救Hira基因敲除细胞中新的H3.3沉积。与同源三聚体复制体组分Ctf4/和-1的结构同源性使得能够绘制平行关系并讨论Hira亚基的同源三聚化状态的功能重要性。Hira组蛋白伴侣复合体与组蛋白变异体H3.3的沉积有关。在这里，作者通过生化和结晶学的方法，报道了Hira亚基的同源三聚作用，这对该复合体的功能活性至关重要。
The HIRA histone chaperone complex deposits the histone variant H3.3 onto chromatin in a DNA synthesis-independent manner. It comprises three identified subunits, HIRA, UBN1 and CABIN1, however the functional oligomerization state of the complex has not been investigated. Here we use biochemical and crystallographic analysis to show that the HIRA subunit forms a stable homotrimer that binds two subunits of CABIN1 in vitro. A HIRA mutant that is defective in homotrimer formation interacts less efficiently with CABIN1, is not enriched at DNA damage sites upon UV irradiation and cannot rescue new H3.3 deposition in HIRA knockout cells. The structural homology with the homotrimeric replisome component Ctf4/AND-1 enables the drawing of parallels and discussion of the functional importance of the homotrimerization state of the HIRA subunit. The HIRA histone chaperone complex is involved in the deposition of the histone variant H3.3. Here the authors, by using biochemical and crystallographic approaches, report the homotrimerization of the HIRA subunit which is critical for the functional activity of the complex.
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影响因子：
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通讯作者：
Almouzni, G
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