Histone H4 K16Q mutation, an acetylation mimic, causes structural disorder of its N-terminal basic patch in the nucleosome.
Histone H4 K16Q mutation, an acetylation mimic, causes structural disorder of its N-terminal basic patch in the nucleosome.
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DOI：
10.1016/j.jmb.2012.04.032
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发表时间：
2012-08-03
影响因子：
5.6
通讯作者：
Bai, Yawen
中科院分区：
文献类型：
--
作者：
Zhou, Bing-Rui;Feng, Hanqiao;Ghirlando, Rodolfo;Kato, Hidenori;Gruschus, James;Bai, Yawen
组蛋白尾部及其翻译后修饰（PTM）在调节染色质的结构和动力学中起着重要作用。对于组蛋白H4，其n端尾部的基本补片K16R17H18R19调节atp依赖性ISWI染色质重塑酶催化的染色质压实和核小体滑动，而H4 K16的乙酰化影响这两种功能。这种乙酰化作用的结构基础尚不清楚。在这里，我们用溶液核磁共振研究了核小体中组蛋白尾部的构象。我们发现组蛋白H2A、H2B和H3的n端尾部的主干酰胺由于其构象紊乱而在很大程度上是可观察到的。然而，H4中仅检测到残基1-15，这表明两个H4组蛋白尾部的残基16-22折叠到核小体核心上。令人惊讶的是，我们发现H4中的K16Q突变（K16乙酰化的模拟物）导致基本斑块的结构紊乱。因此，我们的研究表明，核小体中H4基补丁的折叠结构对于ISWI酶的染色质压实和核小体重塑是重要的，而K16乙酰化通过引起基补丁K16R17H18R19的结构紊乱而影响这两种功能。
Histone tails and their post-translational modifications (PTM) play important roles in regulating the structure and dynamics of chromatin. For histone H4, the basic patch K16R17H18R19 in the N-terminal tail modulates chromatin compaction and nucleosome sliding catalyzed by ATP-dependent ISWI chromatin remodeling enzymes while acetylation of H4 K16 affects both functions. The structural basis for the effects of this acetylation is unknown. Here we investigated the conformation of histone tails in the nucleosome by solution NMR. We found that backbone amides of the N-terminal tails of histones H2A, H2B, and H3 are largely observable due to their conformational disorder. However, only residues 1–15 in H4 can be detected, indicating that residues 16–22 in the tails of both H4 histones fold onto the nucleosome core. Surprisingly, we found that K16Q mutation in H4, a mimic of K16 acetylation, leads to a structural disorder of the basic patch. Thus, our study suggests that the folded structure of the H4 basic patch in the nucleosome is important for chromatin compaction and nucleosome remodeling by ISWI enzymes while K16 acetylation affects both functions by causing structural disorder of the basic patch, K16R17H18R19.
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影响因子：
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作者：
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通讯作者：
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Schuck, P
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