Evidence map›Paper›PMID 36006697›Full record

ArticleThe Journal of clinical investigation2022

CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF.

Marius V Dannappel, Danxi Zhu, Xin Sun, Hui Kheng Chua, Marle Poppelaars, Monica Suehiro, Subash Khadka, Terry Cc Lim Kam Sian, Dhanya Sooraj, Melissa Loi and 6 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Heterozygous Med13l mice recapitulate a developmental growth delay and craniofacial anomalies seen in MED13L syndrome.Developmental dynamics : an official publication of the American Association of Anatomists · 2026
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  11. Targeting super-enhancer activity for colorectal cancer therapy.American journal of translational research · 2024
    Review
  12. Genetically Engineered Mice Unveil In Vivo Roles of the Mediator Complex.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Marius V DannappelCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Danxi ZhuCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Xin SunCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Hui Kheng ChuaCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Marle PoppelaarsCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Monica SuehiroCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Subash KhadkaDepartment of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Terry Cc Lim Kam SianCancer Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology.
Dhanya SoorajCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Melissa LoiCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Hugh GaoCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Daniel CroaghSchool of Clinical Sciences at Monash Health, and.
Roger J DalyCancer Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology.
Pouya FaridiDepartment of Medicine, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
Thomas G BoyerDepartment of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Ron FiresteinCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.

Funding

Molecular basis of MED12 in the pathogenesis of uterine fibroidsR01HD087417 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI THOMAS G BOYER · 2017 to 2026
$3.4M
NICHD NIH HHS R01 HD087417
6 · The paper itself

Abstract

Initiation and maintenance of transcriptional states are critical for controlling normal tissue homeostasis and differentiation. The cyclin dependent kinases CDK8 and CDK19 (Mediator kinases) are regulatory components of Mediator, a highly conserved complex that orchestrates enhancer-mediated transcriptional output. While Mediator kinases have been implicated in the transcription of genes necessary for development and growth, its function in mammals has not been well defined. Using genetically defined models and pharmacological inhibitors, we showed that CDK8 and CDK19 function in a redundant manner to regulate intestinal lineage specification in humans and mice. The Mediator kinase module bound and phosphorylated key components of the chromatin remodeling complex switch/sucrose non-fermentable (SWI/SNF) in intestinal epithelial cells. Concomitantly, SWI/SNF and MED12-Mediator colocalized at distinct lineage-specifying enhancers in a CDK8/19-dependent manner. Thus, these studies reveal a transcriptional mechanism of intestinal cell specification, coordinated by the interaction between the chromatin remodeling complex SWI/SNF and Mediator kinase.

Indexed as

Chromatin Assembly and DisassemblySucroseAnimalsChromatinCyclin-Dependent Kinase 8Cyclin-Dependent KinasesCyclinsHomeostasisHumansMammalsMiceTranscription FactorsCDK19 protein, humanCDK8 protein, humanChromatinCyclin-Dependent Kinase 8Cyclin-Dependent KinasesCyclinsSucroseTranscription FactorsGastroenterologyGeneticsMolecular geneticsMouse modelsOncogenes

Identifiers

PMID36006697
PMCPMC9566890

What OpenQuestion holds

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LicenceCC BY
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.