Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex.
Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex.
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Hat2p 识别组蛋白 H3 尾部，以指定 Hat1p/Hat2p 复合物对新合成的 H3/H4 异二聚体进行乙酰化
DOI：
10.1101/gad.240531.114
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发表时间：
2014-06-01
影响因子：
10.5
通讯作者：
Yang M
中科院分区：
文献类型：
--
作者：
Li Y;Zhang L;Liu T;Chai C;Fang Q;Wu H;Agudelo Garcia PA;Han Z;Zong S;Yu Y;Zhang X;Parthun MR;Chai J;Xu RM;Yang M
组蛋白转录后修饰在复制、转录和DNA修复的调控中起重要作用。关于乙酰转移酶复合物Hat 1 p/Hat 2 p在染色质重塑中的作用仍然存在关键问题。Li等人的高分辨率结构研究揭示了Hat 1 p/Hat 2 p如何识别并促进新组装的组蛋白H3/H4异二聚体上的N-末端赖氨酸残基在其掺入染色质之前的修饰。这项研究描绘了Hat 1 p/Hat 2 p复合物的底物识别机制，这对DNA复制和染色质重塑过程至关重要。组蛋白的翻译后修饰是复制、转录和DNA修复的重要调节因子。特别地，H3/H4异二聚体中新合成的组蛋白H4在其掺入染色质之前在N-末端赖氨酸残基上被乙酰化。以前的研究已经确定，组蛋白乙酰转移酶（HAT）复合物Hat 1 p/Hat 2 p药物这种修饰。然而，Hat 1 p/Hat 2 p如何识别并促进新组装的H3/H4异二聚体的酶活性的机制仍然未知。此外，Hat 2 p是WD 40重复蛋白，其在许多组蛋白修饰物复合物中发现。然而，WD 40重复蛋白如何促进组蛋白修饰酶的酶促活性尚不清楚。在这项研究中，我们首先解决了Hat 1 p/Hat 2 p/CoA/H4肽复合物的高分辨率晶体结构，并发现H4尾与Hat 1 p和Hat 2 p相互作用，从而促进底物募集。我们进一步发现H3 N端肽可以与Hat 2 p WD 40结构域结合，并解决了Hat 1 p/Hat 2 p/CoA/H4/H3肽复合物的结构。此外，与Hat 2 p的相互作用需要未修饰的Arg 2/Lys 4和Lys 9的H3尾部，这表明一种新的模型，以指定Hat 1 p/Hat 2 p对新合成的H3/H4异二聚体的活性。总之，我们的研究证明了Hat 1 p/Hat 2 p复合物的底物识别机制，这对于DNA复制和其他染色质重塑过程至关重要。
Histone post-transcriptional modifications play important roles in the regulation of replication, transcription, and DNA repair. Key questions remain regarding the role of the acetyltransferase complex Hat1p/Hat2p in chromatin remodeling. High-resolution structural studies by Li et al. now reveal how Hat1p/Hat2p recognizes and facilitates the modification of N-terminal lysine residues on the newly assembled histone H3/H4 heterodimer prior to its incorporation into chromatin. This study delineates the mechanism of substrate recognition by the Hat1p/Hat2p complex, which is critical to DNA replication and chromatin remodeling processes. Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the histone acetyltransferase (HAT) complex Hat1p/Hat2p medicates this modification. However, the mechanism of how Hat1p/Hat2p recognizes and facilitates the enzymatic activities on the newly assembled H3/H4 heterodimer remains unknown. Furthermore, Hat2p is a WD40 repeat protein, which is found in many histone modifier complexes. However, how the WD40 repeat proteins facilitate enzymatic activities of histone modification enzymes is unclear. In this study, we first solved the high-resolution crystal structure of a Hat1p/Hat2p/CoA/H4 peptide complex and found that the H4 tail interacts with both Hat1p and Hat2p, by which substrate recruitment is facilitated. We further discovered that H3 N-terminal peptides can bind to the Hat2p WD40 domain and solved the structure of the Hat1p/Hat2p/CoA/H4/H3 peptide complex. Moreover, the interaction with Hat2p requires unmodified Arg2/Lys4 and Lys9 on the H3 tail, suggesting a novel model to specify the activity of Hat1p/Hat2p toward newly synthesized H3/H4 heterodimers. Together, our study demonstrated the substrate recognition mechanism by the Hat1p/Hat2p complex, which is critical for DNA replication and other chromatin remodeling processes.
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影响因子：
4
作者：
Brownell, JE;Allis, CD
通讯作者：
Allis, CD
影响因子：
56.9
作者：
Nakayam, J;Rice, JC;Grewal, SIS
通讯作者：
Grewal, SIS
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444902016657
发表时间：
2002-11-01
影响因子：
2.2
作者：
Adams, PD;Grosse-Kunstleve, RW;Terwilliger, TC
通讯作者：
Terwilliger, TC
影响因子：
16.8
作者：
Couture, Jean-Francois;Collazo, Evys;Trievel, Raymond C.
通讯作者：
Trievel, Raymond C.