Evidence map›Paper›PMID 31402173›Full record

ArticleCell2019

A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers.

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 and 14 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

151 citing papers in PubMed, 270 citations in OpenAlex.

  1. Article
  2. Article
  3. The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026
    Review
  4. Review
  5. Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Resolving Sub-Nuclear Architecture from Compartments to Functional Domains.International journal of molecular sciences · 2026
    Review
  11. Article
  12. Article
  13. Med14 phosphorylation shapes genomic response to GLP-1 agonists.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

91 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 2 countries.

Laila El KhattabiLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Haiyan ZhaoDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora CO 80045, USA.
Jens KalchschmidtLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Natalie YoungDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora CO 80045, USA.
Seolkyoung JungLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Peter Van BlerkomDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora CO 80045, USA.
Philippe Kieffer-KwonLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Kyong-Rim Kieffer-KwonLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Solji ParkLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Xiang WangLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Jordan KrebsLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Subhash TripathiLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Noboru SakabeDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
Débora R SobreiraDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
Su-Chen HuangThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
Suhas S P RaoThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nathanael PruettLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Daniel ChaussLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Erica SadlerLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Andrea LopezLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Marcelo A NóbregaDepartment of Human Genetics, University of Chicago, Chicago, IL, USA.
Erez Lieberman AidenThe Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
Francisco J AsturiasDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora CO 80045, USA. Electronic address: francisco.asturias@ucdenver.edu.
Rafael CasellasLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA; Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: rafael.casellas@nih.gov.
National Institute of Arthritis and Musculoskeletal and Skin Diseases · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Chicago · USBaylor College of Medicine · USStanford University · US

Funding

STRUCTURAL STUDIES OF EUKARYOTIC TRANSCRIPTIONR01GM067167 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ASTURIAS, FRANCISCO J · 2003 to 2025
$9.2M
GENOME WIDE MAPPING OF LOOPS USING IN SITU HI-CUM1HG009375 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI LIEBERMAN-AIDEN, EREZ · 2017 to 2021
$4.7M
Exploring how the genome folds through proximity ligation and sequencingDP2OD008540 · OD · BROAD INSTITUTE, INC. · PI LIEBERMAN-AIDEN, EREZ · 2011 to 2016
$3.0M
NHGRI NIH HHS UM1 HG009375NIGMS NIH HHS R01 GM067167NIH HHS DP2 OD008540
6 · The paper itself

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 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.

Indexed as

AnimalsCD4-Positive T-LymphocytesCell Cycle ProteinsCells, CulturedChromosomal Proteins, Non-HistoneCohesinsCRISPR-Cas SystemsCryoelectron MicroscopyEnhancer Elements, GeneticGene EditingHumansMaleMediator ComplexMiceMice, Inbred C57BLMouse Embryonic Stem CellsCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsMediator ComplexRNA Polymerase IISaccharomyces cerevisiae Proteins

Identifiers

PMID31402173
PMCPMC7533040
OpenAlexW2967977322

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.