Set2-mediated H3K36 methylation states redundantly repress the production of antisense transcripts: role in transcription regulation.
Set2-mediated H3K36 methylation states redundantly repress the production of antisense transcripts: role in transcription regulation.
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DOI：
10.1002/2211-5463.13226
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发表时间：
2021-08
期刊：
影响因子：
2.6
通讯作者：
Du HN
中科院分区：
文献类型：
--
作者：
Mei YC;Feng J;He F;Li YM;Liu Y;Li F;Chen Y;Du HN
甲基转移酶 Set2 介导的组蛋白 H3 赖氨酸 36 (H3K36) 甲基化涉及在该位点添加最多三个甲基，已被证明在许多染色质偶联事件中发挥作用。已知 H3K36 的甲基化会招募不同的染色质效应蛋白，影响转录、mRNA 剪接和 DNA 修复。在这项研究中，我们设计了两种分别缺乏 H3K36 单/二甲基化 (H3K36me1/2) 和三甲基化 (H3K36me3) 的酵母 set2 突变体，并表征了它们在营养丰富的条件下产生反义转录本的作用。使用我们新的生物信息学识别管道分析，我们能够在 set2Δ 细胞中识别出比之前发表的更多的反义转录本。我们进一步表明 H3K36me1/2 或 H3K36me3 过度抑制反义转录本的产生。此外，基因本体（GO）分析表明H3K36me3介导的反义转录可能在DNA复制和DNA损伤修复中发挥作用，这独立于相应有义基因表达的调节。总的来说，我们的结果验证了不同 H3K36 甲基化状态的共同调节机制，特别是在反义转录的抑制方面。使用新的生物信息学识别管道分析，在营养丰富的条件下，在 Set2 缺陷细胞中鉴定出数千个反义转录本，这些转录本是从正义基因的相反链转录的，并且通常在野生型细胞中沉默。通过设计两个单位点突变，我们发现 H3K36me1/2 或 H3K36me3 冗余抑制反义转录本，这表明不同 H3K36 甲基化状态的共调节机制。
Methyltransferase Set2‐mediated methylation of histone H3 lysine 36 (H3K36), which involves the addition of up to three methyl groups at this site, has been demonstrated to function in many chromatin‐coupled events. The methylation of H3K36 is known to recruit different chromatin effector proteins, affecting transcription, mRNA splicing and DNA repair. In this study, we engineered two yeast set2 mutants that lack H3K36 mono/dimethylation (H3K36me1/2) and trimethylation (H3K36me3), respectively, and characterized their roles in the production of antisense transcripts under nutrient‐rich conditions. Using our new bioinformatics identification pipeline analysis, we are able to identify a larger number of antisense transcripts in set2∆ cells than has been published previously. We further show that H3K36me1/2 or H3K36me3 redundantly repressed the production of antisense transcripts. Moreover, gene ontology (GO) analysis implies that H3K36me3‐mediated antisense transcription might play a role in DNA replication and DNA damage repair, which is independent of regulation of the corresponding sense gene expression. Overall, our results validate a coregulatory mechanism of different H3K36 methylation states, particularly in the repression of antisense transcription. Using a new bioinformatics identification pipeline analysis, thousands of antisense transcripts are identified in Set2‐deficient cells under nutrient‐rich conditions, which are transcribed from the opposite strand of sense genes and usually silenced in wild‐type cells. By engineering two single‐site mutations, we show that H3K36me1/2 or H3K36me3 redundantly repressed antisense transcripts, which suggests a coregulatory mechanism of different H3K36 methylation states.
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影响因子：
64.8
作者：
Carrieri, Claudia;Cimatti, Laura;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
16
作者：
Lee, Chul-Hwan;Wu, Jun;Li, Bing
通讯作者：
Li, Bing
影响因子：
8.8
作者：
McDaniel SL;Hepperla AJ;Huang J;Dronamraju R;Adams AT;Kulkarni VG;Davis IJ;Strahl BD
通讯作者：
Strahl BD
DOI：
10.1007/s00018-017-2517-x
发表时间：
2017-09
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
McDaniel SL;Strahl BD
通讯作者：
Strahl BD
影响因子：
64.5
作者：
Ozsolak F;Kapranov P;Foissac S;Kim SW;Fishilevich E;Monaghan AP;John B;Milos PM
通讯作者：
Milos PM