Unique and Shared Roles for Histone H3K36 Methylation States in Transcription Regulation Functions
Unique and Shared Roles for Histone H3K36 Methylation States in Transcription Regulation Functions
复制标题
组蛋白 H3K36 甲基化状态在转录调控功能中的独特和共同作用
DOI：
10.1016/j.celrep.2020.107751
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发表时间：
2020-06-09
期刊：
影响因子：
8.8
通讯作者：
Strahl, Brian D.
中科院分区：
文献类型：
--
作者：
DiFiore, Julia, V;Ptacek, Travis S.;Strahl, Brian D.
Set 2共转录甲基化组蛋白H3的赖氨酸36（H3 K36），产生单-，二-和三甲基化（H3 K36 me 1/2/3）。这些修饰募集或排斥对转录保真度、mRNA剪接和DNA修复重要的染色质效应蛋白。然而，目前尚不清楚H3 K36的不同甲基化状态是否具有不同的生物学功能。在这里，我们使用Set 2的工程形式，产生不同的赖氨酸甲基化状态，以确定H3 K36修饰的独特和共享功能。虽然H3 K36 me 1/2和H3 K36 me 3在许多SET 2缺失表型中是功能冗余的，但我们发现H3 K36 me 3具有与Bur 1激酶活性和FACT（促进染色质转录）复合物功能相关的独特功能。此外，在营养胁迫期间，H3 K36 me 1/2或H3 K36 me 3抑制高水平的组蛋白乙酰化和基因内产生的隐蔽转录。我们的研究结果揭示了不同的H3 K36甲基化状态对不同染色质功能的调节潜力。
Set2 co-transcriptionally methylates lysine 36 of histone H3 (H3K36), producing mono-, di-, and trimethylation (H3K36me1/2/3). These modifications recruit or repel chromatin effector proteins important for transcriptional fidelity, mRNA splicing, and DNA repair. However, it was not known whether the different methylation states of H3K36 have distinct biological functions. Here, we use engineered forms of Set2 that produce different lysine methylation states to identify unique and shared functions for H3K36 modifications. Although H3K36me1/2 and H3K36me3 are functionally redundant in many SET2 deletion phenotypes, we found that H3K36me3 has a unique function related to Bur1 kinase activity and FACT (facilitates chromatin transcription) complex function. Further, during nutrient stress, either H3K36me1/2 or H3K36me3 represses high levels of histone acetylation and cryptic transcription that arises from within genes. Our findings uncover the potential for the regulation of diverse chromatin functions by different H3K36 methylation states.