小柯机器人

以色列魏茨曼科学研究所Naama Barkai和Gilad Yaakov研究组用酵母中的基因编码交换计时器测量组蛋白置换动力学。该项研究成果发表在2021年7月8日出版的《自然—生物技术》杂志上。

为了克服传统脉冲追踪组蛋白标记较差的时间分辨率问题，他们提出了一种基因编码的组蛋白交换计时器，该计时器对两个标记的组蛋白亚基共同驻留在单个基因组位点的持续时间敏感。他们将这些传感器应用于单个样本绘制的酵母组蛋白交换的全基因组模式。比较循环和 G1 停滞细胞中的 H3 交换表明，每分钟数百个核小体（<所有核小体的 1%）发生独立于复制的 H3 交换，组蛋白启动子的速率最大。

他们观察到两个核小体核心亚复合体之间的显著差异：H2A-H2B 亚复合体在编码区域内经历快速转录依赖性替换，而 H3-H4 替换主要发生在启动子核小体内，与基因激活或抑制相关。他们的计时器允许以分钟的时间尺度分辨率对组蛋白交换动力学进行体内研究。

研究人员表示，携带特定位置标记的组蛋白和带有一般标记的组蛋白之间的组蛋白交换对于基因调控很重要，但对组蛋白交换的理解仍然不完整。

附：英文原文

Title: Measurement of histone replacement dynamics with genetically encoded exchange timers in yeast

Author: Gilad Yaakov, Felix Jonas, Naama Barkai

Issue&Volume: 2021-07-08

Abstract: Histone exchange between histones carrying position-specific marks and histones bearing general marks is important for gene regulation, but understanding of histone exchange remains incomplete. To overcome the poor time resolution of conventional pulse–chase histone labeling, we present a genetically encoded histone exchange timer sensitive to the duration that two tagged histone subunits co-reside at an individual genomic locus. We apply these sensors to map genome-wide patterns of histone exchange in yeast using single samples. Comparing H3 exchange in cycling and G1-arrested cells suggests that replication-independent H3 exchange occurs at several hundred nucleosomes (<1% of all nucleosomes) per minute, with a maximal rate at histone promoters. We observed substantial differences between the two nucleosome core subcomplexes: H2A-H2B subcomplexes undergo rapid transcription-dependent replacement within coding regions, whereas H3-H4 replacement occurs predominantly within promoter nucleosomes, in association with gene activation or repression. Our timers allow the in vivo study of histone exchange dynamics with minute time scale resolution.

DOI: 10.1038/s41587-021-00959-8

Source: https://www.nature.com/articles/s41587-021-00959-8

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
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