瑞士巴塞尔大学 Filippo M. Rijli团队发现，在发育过程中，一种独特的双向多梳结构调节刺激反应转录。该项研究成果发表在2021年2月18日出版的《自然-遗传学》上。

研究人员发现在发育感觉神经元中，围产期感觉活动依赖性诱导之前，即刻早期基因被嵌入到具有独特二分体多梳结构的染色质中，在启动子区域具有活性H3K27ac标记，而在基因体上则带有抑制性Ezh2调控的H3K27me3标记。这种双向特征广泛存在于发育的细胞类型中，包括胚胎干细胞。基因体的多梳状标记抑制了mRNA的延伸并阻碍了有效转录，同时仍然有利于快速依赖刺激标记的去除和二分基因的诱导。

该研究揭示了发育的表观遗传机制，调节对相关刺激转录反应的速度和幅度，同时防止不适当刺激激活基因转录。

据悉，细胞对环境刺激的快速反应是发育和成熟的基础。即刻早期基因可以在数分钟内响应各种信号开启转录。人们对如何调节其诱导水平以及如何在发育过程中防止杂散信号过早地激活其转录的了解很少。

附：英文原文

Title: A unique bipartite Polycomb signature regulates stimulus-response transcription during development

Author: Taro Kitazawa, Dania Machlab, Onkar Joshi, Nicola Maiorano, Hubertus Kohler, Sebastien Ducret, Sandra Kessler, Henrik Gezelius, Charlotte Soneson, Panagiotis Papasaikas, Guillermina Lpez-Bendito, Michael B. Stadler, Filippo M. Rijli

Issue&Volume: 2021-02-18

Abstract: Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes. Immediate early genes in developing sensory neurons have a unique bipartite chromatin signature: H3K27ac on promoters and enhancers, and H3K27me3 on gene bodies. Polycomb marking of gene bodies inhibits productive mRNA elongation.

DOI: 10.1038/s41588-021-00789-z

Source: https://www.nature.com/articles/s41588-021-00789-z