Analysis of the Histone H3.1 Interactome: A Suitable Chaperone for the Right Event.
Analysis of the Histone H3.1 Interactome: A Suitable Chaperone for the Right Event.
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DOI：
10.1016/j.molcel.2015.08.005
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发表时间：
2015-11-19
期刊：
影响因子：
16
通讯作者：
Reinberg D
中科院分区：
文献类型：
--
作者：
Campos EI;Smits AH;Kang YH;Landry S;Escobar TM;Nayak S;Ueberheide BM;Durocher D;Vermeulen M;Hurwitz J;Reinberg D
尽管在序列水平上差异最小，但哺乳动物H3变体与不同的多肽组结合。虽然组蛋白H3.1在循环细胞中占主导地位，但我们对它在沉积途中或从染色质驱逐后形成的可溶性复合物的了解仍然有限。在这里，我们提供了一个全面的分析H3.1结合蛋白质组，强调其与组蛋白伴侣和复制叉组件的相互作用。定量质谱分析揭示了170种蛋白质相互作用，而H3.1和相关酶活性的大规模生物化学分级分离揭示了分裂的人类细胞中超过20种稳定的蛋白质复合物。sNASP和ASF1分子伴侣在可溶性组蛋白的加工中起关键作用，但不与活性的CDC 45/MCM2 - 7/GINS（CMG）复制解旋酶相关。我们还发现TONSL-MMS22L作为H3-H4组蛋白伴侣发挥作用。它与复制解旋酶的调节MCM5亚基相关。
Despite minimal disparity at the sequence level, mammalian H3 variants bind to distinct sets of polypeptides. Though histone H3.1 predominates in cycling cells, our knowledge of the soluble complexes that it forms en route to deposition or following eviction from chromatin remains limited. Here, we provide a comprehensive analysis of the H3.1-binding proteome, with emphasis on its interactions with histone chaperones and components of the replication fork. Quantitative mass spectrometry revealed 170 protein interactions, whereas a large-scale biochemical fractionation of H3.1 and associated enzymatic activities uncovered over twenty stable protein complexes in dividing human cells. The sNASP and ASF1 chaperones play pivotal roles in the processing of soluble histones, but do not associate with the active CDC45/MCM2-7/GINS (CMG) replicative helicase. We also find TONSL-MMS22L to function as a H3-H4 histone chaperone. It associates with the regulatory MCM5 subunit of the replicative helicase.