Evidence map›Paper›PMID 33176148›Full record

ArticleCell reports2020

ARID1A Mutations Promote P300-Dependent Endometrial Invasion through Super-Enhancer Hyperacetylation.

Mike R Wilson, Jake J Reske, Jeanne Holladay, Subechhya Neupane, Julie Ngo, Nina Cuthrell, Marc Wegener, Mary Rhodes, Marie Adams, Rachael Sheridan and 10 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 58 citations in OpenAlex.

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  20. The roles of chromatin regulatory factors in endometriosis.Journal of assisted reproduction and genetics · 2024
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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

20 authors at 6 institutions in 3 countries.

Mike R WilsonDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Jake J ReskeDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Jeanne HolladayDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Subechhya NeupaneDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Julie NgoDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Nina CuthrellDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Marc WegenerGenomics Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Mary RhodesGenomics Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Marie AdamsGenomics Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Rachael SheridanFlow Cytometry Core, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Galen HostetterPathology and Biorepository Core, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Fahad T AlotaibiDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; Department of Physiology, College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
Paul J YongDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
Michael S AnglesioDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, Vancouver General Hospital, and BC Cancer, Vancouver, BC, Canada.
Bruce A LesseyDepartment of Obstetrics and Gynecology, Wake Forest Baptist Health, Winston-Salem, NC 27157, USA.
Richard E LeachDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Department of Women's Health, Spectrum Health System, Grand Rapids, MI 49341, USA.
Jose M TeixeiraDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Department of Women's Health, Spectrum Health System, Grand Rapids, MI 49341, USA.
Stacey A MissmerDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Department of Women's Health, Spectrum Health System, Grand Rapids, MI 49341, USA.
Asgerally T FazleabasDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Department of Women's Health, Spectrum Health System, Grand Rapids, MI 49341, USA.
Ronald L ChandlerDepartment of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Department of Women's Health, Spectrum Health System, Grand Rapids, MI 49341, USA; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA. Electronic address: rlc@msu.edu.
Michigan State University · USVan Andel Institute · USSpectrum Health · USUniversity of British Columbia · CAAtrium Health Wake Forest Baptist · USBC Cancer Agency · CA

Funding

Patient-specific targeting of uterine fibroidsR01HD096259 · NICHD · MICHIGAN STATE UNIVERSITY · PI TEIXEIRA, JOSE M. · 2019 to 2023
$2.4M
Epigenetic regulatory mechanisms and therapeutic opportunities in endometriosisR01HD103617 · NICHD · MICHIGAN STATE UNIVERSITY · PI CHANDLER, RONALD L · 2021 to 2025
$1.7M
Role of chromatin remodeling and cell signaling in endometriosis etiologyR21HD099383 · NICHD · MICHIGAN STATE UNIVERSITY · PI CHANDLER, RONALD L · 2019 to 2020
$430k
NICHD NIH HHS R01 HD096259NICHD NIH HHS R01 HD103617NICHD NIH HHS R21 HD099383
6 · The paper itself

Abstract

Endometriosis affects 1 in 10 women and is characterized by the presence of abnormal endometrium at ectopic sites. ARID1A mutations are observed in deeply invasive forms of the disease, often correlating with malignancy. To identify epigenetic dependencies driving invasion, we use an unbiased approach to map chromatin state transitions accompanying ARID1A loss in the endometrium. We show that super-enhancers marked by high H3K27 acetylation are strongly associated with ARID1A binding. ARID1A loss leads to H3K27 hyperacetylation and increased chromatin accessibility and enhancer RNA transcription at super-enhancers, but not typical enhancers, indicating that ARID1A normally prevents super-enhancer hyperactivation. ARID1A co-localizes with P300 at super-enhancers, and genetic or pharmacological inhibition of P300 in ARID1A mutant endometrial epithelia suppresses invasion and induces anoikis through the rescue of super-enhancer hyperacetylation. Among hyperactivated super-enhancers, SERPINE1 (PAI-1) is identified as an essential target gene driving ARID1A mutant endometrial invasion. Broadly, our findings provide rationale for therapeutic strategies targeting super-enhancers in ARID1A mutant endometrium.

Indexed as

AcetylationAnimalsDNA-Binding ProteinsEndometriosisEndometriumFemaleHumansMiceMutationRabbitsRatsTranscription FactorsARID1A protein, humanDNA-Binding ProteinsTranscription FactorsARID1AendometriosisendometriuminvasionP300PAI-1SERPINE1super-enhancerSWI/SNF

Identifiers

PMID33176148
PMCPMC7682620
OpenAlexW3101617773

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.