Spt5介导的增强子转录直接偶联增强子激活与启动
网站公告: 诚信为本,市场永远在变,诚信永远不变
咨询热线

+86-0000-96877

THE LATEST INFORMATION

| 资讯中心 |

Spt5介导的增强子转录直接偶联增强子激活与启动

时间:2020-04-13  点击量:
更多

本期文章:《自然—遗传学》:Online/在线发表

近日,奥地利分子病理研究所Rushad Pavri课题组发现,Spt5介导的增强子转录直接偶联增强子激活与启动子相互作用。相关论文于2020年4月6日在线发表在《自然—遗传学》杂志上。

活跃的增强子经常被转录,但是增强子转录的调节作用仍然存在争议。通过敲低激活小鼠B细胞中RNA聚合酶II的暂停和延伸因子Spt5,研究人员发现大约50%的增强子-基因对显示出共同调控的转录,这与增强子转录的潜在功能一致。

 

具体而言,Spt5敲低导致免疫球蛋白重链基因座(Igh)失去了增强子-启动子的物理相互作用和基因表达,从而阻碍了抗体类别转换的重组。该缺陷与增强子转录的丧失紧密相关,但不影响组蛋白H3第27位赖氨酸的乙酰化、染色质可及性以及增强子上中介体和cohesin 的占位。

 

令人惊讶的是,Spt5敲低细胞中CRISPRa介导的增强子转录的回补恢复了Igh基因的表达。这些工作表明,Spt5介导的增强子转录是活跃增强子及其靶启动子之间的物理和功能相互作用的基础。

 

附:英文原文

Title: Spt5-mediated enhancer transcription directly couples enhancer activation with physical promoter interaction

Author: Johanna Fitz, Tobias Neumann, Monika Steininger, Eva-Maria Wiedemann, Adriana Cantoran Garcia, Alexander Athanasiadis, Ursula E. Schoeberl, Rushad Pavri

Issue&Volume: 2020-04-06

Abstract: Active enhancers are frequently transcribed, yet the regulatory role of enhancer transcription remains debated. Here, we depleted the RNA polymerase II pausing and elongation factor Spt5 in activated mouse B cells and found that approximately 50% of enhancer–gene pairs showed co-regulated transcription, consistent with a potential functional requirement for enhancer transcription. In particular, Spt5 depletion led to loss of super-enhancer–promoter physical interaction and gene expression at the immunoglobulin heavy-chain locus (Igh), abrogating antibody class switch recombination. This defect correlated strictly with loss of enhancer transcription but did not affect acetylation of histone H3 at lysine 27, chromatin accessibility and occupancy of Mediator and cohesin at the enhancer. Strikingly, CRISPRa-mediated rescue of enhancer transcription in Spt5-depleted cells restored Igh gene expression. Our work suggests that Spt5-mediated enhancer transcription underlies the physical and functional interaction between a subset of active enhancers and their target promoters.

DOI: 10.1038/s41588-020-0605-6

Source: https://www.nature.com/articles/s41588-020-0605-6

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex

地址:这里是您的公司地址   电话:+86-0000-96877    Copyright © 2002-2019 电竞平台 版权所有   
技术支持:织梦58[织梦58]   ICP备案编号:琼ICP备14001732号   统计代码放置
网站地图(百度 / 谷歌
这里是您的网站名称