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.

中文翻译：

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Set2 甲基转移酶的光遗传学开关为 H3K36 甲基化的转录依赖性和非转录依赖性动力学提供了证据


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。尽管已经研究了 H3K36 甲基化的影响，但 H3K36me 沉积和去除的全基因组动态尚不清楚。我们通过将 Set2（酵母中唯一的 H3K36 甲基转移酶）与光激活核穿梭 (LANS) 结构域融合，为 Set2 建立了快速、可逆的光遗传学控制。光激活导致有效的 Set2-LANS 核定位，随后 H3K36me3 在体内沉积，总 H3K36me3 水平与 RNA 丰度相关。尽管基因显示出不同的 H3K36 甲基化水平，但 H3K36me3 积累的相对速率在很大程度上是线性的并且在基因之间保持一致，这表明 H3K36me3 沉积以定向方式发生在所有转录基因上，无论其总体转录频率如何。 H3K36me3 的去除高度依赖于去甲基化酶 Rph1。然而，每个基因的 H3K36me3 丢失率与 RNA 丰度相关性较弱，并呈指数衰减，表明 H3K36 去甲基酶以全局、随机的方式发挥作用。总而言之，这些数据提供了 H3K36 甲基化和去甲基化的详细时间视图，分别表明 H3K36me 沉积和去除的转录依赖性和独立机制。