英国 MRC 伦敦医学科学研究所 (LMS) Petra Hajkova研究组近日取得一项新成果。他们发现性别特异性染色质重塑保障生殖细胞的转录。2021年12月8日出版的《自然》杂志发表了这项成果。

他们使用超低输入的天然染色质免疫沉淀方法，表明在 DNA 去甲基化后，性腺原始生殖细胞经历了抑制性组蛋白修饰的重塑，从而使小鼠产生了性别特异性特征。他们进一步证明 Polycomb 在新低甲基化生殖系基因组的转录控制中具有核心作用，因为 Ezh2 的遗传缺失导致异常转录激活、逆转录转座子去抑制和发育中的雌性生殖细胞的显著丧失。Ezh2 缺失的性别特异性效应可以通过在雄性和雌性生殖细胞中观察到的抑制性修饰的独特景观来解释。总体而言，他们的研究提供了对发育重编程系统背景下抑制性染色质修饰之间动态相互作用的洞察。

研究人员表示，表观遗传景观的稳定性是维持细胞类型特异性转录谱的基础。作为主要的抑制表观遗传系统之一，DNA 甲基化已被证明对长期基因沉默很重要。它的丢失导致分化细胞和癌症中的异位和异常转录。在缺乏广泛转录激活的情况下，发育中的小鼠种系能够承受 DNA 甲基化的整体变化。

附：英文原文

Title: Sex-specific chromatin remodelling safeguards transcription in germ cells

Author: Huang, Tien-Chi, Wang, Yi-Fang, Vazquez-Ferrer, Eric, Theofel, Ina, Requena, Cristina E., Hanna, Courtney W., Kelsey, Gavin, Hajkova, Petra

Issue&Volume: 2021-12-08

Abstract: Stability of the epigenetic landscape underpins maintenance of the cell-type-specific transcriptional profile. As one of the main repressive epigenetic systems, DNA methylation has been shown to be important for long-term gene silencing; its loss leads to ectopic and aberrant transcription in differentiated cells and cancer1. The developing mouse germ line endures global changes in DNA methylation in the absence of widespread transcriptional activation. Here, using an ultra-low-input native chromatin immunoprecipitation approach, we show that following DNA demethylation the gonadal primordial germ cells undergo remodelling of repressive histone modifications, resulting in a sex-specific signature in mice. We further demonstrate that Polycomb has a central role in transcriptional control in the newly hypomethylated germline genome as the genetic loss of Ezh2 leads to aberrant transcriptional activation, retrotransposon derepression and dramatic loss of developing female germ cells. This sex-specific effect of Ezh2 deletion is explained by the distinct landscape of repressive modifications observed in male and female germ cells. Overall, our study provides insight into the dynamic interplay between repressive chromatin modifications in the context of a developmental reprogramming system.

DOI: 10.1038/s41586-021-04208-5

Source: https://www.nature.com/articles/s41586-021-04208-5