期刊
CELL
卷 178, 期 5, 页码 1145-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.07.011
关键词
-
资金
- NIH Helix Systems
- NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
- NIGMS (National Institute of General Medical Sciences) [R01-67167]
- NIH [1DP2OD008540-01, UM1HG009375]
- NSF [PHY-1427654]
- Welch Foundation [Q-1866]
- NVIDIA Research Center Award
- IBM University Challenge
- Google Research
- Cancer Prevention Research Institute of Texas Scholar Award [R1304]
- McNair Medical Institute
- President's Early Career Award in Science and Engineering
While Mediator plays a key role in eukaryotic transcription, little is known about its mechanism of action. This study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-EM) to dissect the function and structure of mammalian Mediator (mMED). Deletion analyses in B, T, and embryonic stem cells (ESC) identified a core of essential subunits required for Pol II recruitment genome-wide. Conversely, loss of non-essential subunits mostly affects promoters linked to multiple enhancers. Contrary to current models, however, mMED and Pol II are dispensable to physically tether regulatory DNA, a topological activity requiring architectural proteins. Cryo-EM analysis revealed a conserved core, with non-essential subunits increasing structural complexity of the tail module, a primary transcription factor target. Changes in tail structure markedly increase Pol II and kinase module interactions. We propose that Mediator's structural pliability enables it to integrate and transmit regulatory signals and act as a functional, rather than an architectural bridge, between promoters and enhancers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据