An optogenetic switch for the Set2 methyltransferase provides evidence for transcription-dependent and -independent dynamics of H3K36 methylation.
An optogenetic switch for the Set2 methyltransferase provides evidence for transcription-dependent and -independent dynamics of H3K36 methylation.
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DOI：
10.1101/gr.264283.120
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发表时间：
2020-11
期刊：
影响因子：
7
通讯作者：
Strahl BD
中科院分区：
文献类型：
--
作者：
Lerner AM;Hepperla AJ;Keele GR;Meriesh HA;Yumerefendi H;Restrepo D;Zimmerman S;Bear JE;Kuhlman B;Davis IJ;Strahl BD
组蛋白H3赖氨酸36甲基化(H3K36me)是一种与转录和DNA修复相关的保守组蛋白修饰。虽然已经研究了H3K36甲基化的影响，但H3K36me沉积和移除的全基因组动力学尚不清楚。我们通过将酵母中唯一的H3K36甲基转移酶Set2与光激活的核穿梭(LANS)结构域融合，建立了快速和可逆光遗传控制。光激活导致Set2-LANS核有效定位，随后H3K36me3在体内沉积，总H3K36me3水平与RNA丰度相关。尽管基因表现出不同水平的H3K36甲基化，但H3K36me3的相对积累率在很大程度上是线性的，并且在基因之间是一致的，这表明H3K36me3在所有转录基因上以一种直接的方式发生，无论它们的总转录频率如何。H3K36me3的去除高度依赖于去甲基酶Rph1。然而，H3K36me3的每个基因丢失率与RNA丰度呈指数衰减关系，这表明H3K36去甲基酶的作用是全球性的、随机的。总之，这些数据提供了H3K36甲基化和去甲基化的详细时间视图，表明H3K36me的沉积和去除分别依赖于转录和独立的机制。
Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification associated with transcription and DNA repair. Although the effects of H3K36 methylation have been studied, the genome-wide dynamics of H3K36me deposition and removal are not known. We established rapid and reversible optogenetic control for Set2, the sole H3K36 methyltransferase in yeast, by fusing the enzyme with the light-activated nuclear shuttle (LANS) domain. Light activation resulted in efficient Set2-LANS nuclear localization followed by H3K36me3 deposition in vivo, with total H3K36me3 levels correlating with RNA abundance. Although genes showed disparate levels of H3K36 methylation, relative rates of H3K36me3 accumulation were largely linear and consistent across genes, suggesting that H3K36me3 deposition occurs in a directed fashion on all transcribed genes regardless of their overall transcription frequency. Removal of H3K36me3 was highly dependent on the demethylase Rph1. However, the per-gene rate of H3K36me3 loss weakly correlated with RNA abundance and followed exponential decay, suggesting H3K36 demethylases act in a global, stochastic manner. Altogether, these data provide a detailed temporal view of H3K36 methylation and demethylation that suggests transcription-dependent and -independent mechanisms for H3K36me deposition and removal, respectively.
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影响因子：
16
作者：
Joshi, AA;Struhl, K
通讯作者：
Struhl, K
影响因子：
64.5
作者：
Keogh, MC;Kurdistani, SK;Krogan, NJ
通讯作者：
Krogan, NJ
影响因子：
4.8
作者：
Kim, TaeSoo;Buratowski, Stephen
通讯作者：
Buratowski, Stephen
影响因子：
64.5
作者：
Carrozza, MJ;Li, B;Workman, JL
通讯作者：
Workman, JL
DOI：
10.1038/nrg3173
发表时间：
2012-04-03
期刊：
Nature reviews. Genetics
影响因子：
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作者：
通讯作者：
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