Mediator of RNA polymerase II transcription subunit 14 / Mediator of RNA polymerase II transcription subunit 22 / Mediator of RNA polymerase II transcription subunit 16 / Mediator of RNA polymerase II transcription subunit 23 / Mediator of RNA polymerase II transcription subunit 19 / Mediator of RNA polymerase II transcription subunit 25 / Mediator of RNA polymerase II transcription subunit 17 / Mediator of RNA polymerase II transcription subunit 9 / Mediator of RNA polymerase II transcription subunit 28 / Mediator of RNA polymerase II transcription subunit 6 ...Mediator of RNA polymerase II transcription subunit 14 / Mediator of RNA polymerase II transcription subunit 22 / Mediator of RNA polymerase II transcription subunit 16 / Mediator of RNA polymerase II transcription subunit 23 / Mediator of RNA polymerase II transcription subunit 19 / Mediator of RNA polymerase II transcription subunit 25 / Mediator of RNA polymerase II transcription subunit 17 / Mediator of RNA polymerase II transcription subunit 9 / Mediator of RNA polymerase II transcription subunit 28 / Mediator of RNA polymerase II transcription subunit 6 / Mediator of RNA polymerase II transcription subunit 15 / Mediator of RNA polymerase II transcription subunit 24 / Mediator of RNA polymerase II transcription subunit 21 / Mediator of RNA polymerase II transcription subunit 4 / Mediator of RNA polymerase II transcription subunit 30 / Mediator of RNA polymerase II transcription subunit 10 / Mediator of RNA polymerase II transcription subunit 31 / Mediator of RNA polymerase II transcription subunit 18 / Mediator of RNA polymerase II transcription subunit 7 / Mediator of RNA polymerase II transcription subunit 8 / Mediator of RNA polymerase II transcription subunit 11 / Mediator of RNA polymerase II transcription subunit 27 / Mediator of RNA polymerase II transcription subunit 29 / Mediator of RNA polymerase II transcription subunit 20 Similarity search - Component
Biological species
Mus musculus (house mouse) / Mouse (mice)
Method
single particle reconstruction / cryo EM / Resolution: 4.02 Å
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01-67167
United States
National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS)
United States
Citation
Journal: Cell / Year: 2019 Title: A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers. Authors: Laila El Khattabi / Haiyan Zhao / Jens Kalchschmidt / Natalie Young / Seolkyoung Jung / Peter Van Blerkom / Philippe Kieffer-Kwon / Kyong-Rim Kieffer-Kwon / Solji Park / Xiang Wang / Jordan ...Authors: Laila El Khattabi / Haiyan Zhao / Jens Kalchschmidt / Natalie Young / Seolkyoung Jung / Peter Van Blerkom / Philippe Kieffer-Kwon / Kyong-Rim Kieffer-Kwon / Solji Park / Xiang Wang / Jordan Krebs / Subhash Tripathi / Noboru Sakabe / Débora R Sobreira / Su-Chen Huang / Suhas S P Rao / Nathanael Pruett / Daniel Chauss / Erica Sadler / Andrea Lopez / Marcelo A Nóbrega / Erez Lieberman Aiden / Francisco J Asturias / Rafael Casellas / Abstract: 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 ...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.
History
Deposition
Mar 4, 2020
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Header (metadata) release
Mar 10, 2021
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Map release
Mar 10, 2021
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Update
Mar 10, 2021
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Current status
Mar 10, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: PELCO Ultrathin Carbon with Lacey Carbon / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 30.0 nm / Pretreatment - Type: PLASMA CLEANING
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