Evidence map›Paper›PMID 36823213›Full record

ArticleCommunications biology2023

MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming.

Wazim Mohammed Ismail, Amelia Mazzone, Flavia G Ghiraldini, Jagneet Kaur, Manvir Bains, Amik Munankarmy, Monique S Bagwell, Stephanie L Safgren, John Moore-Weiss, Marina Buciuc and 15 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Unlocking Lung Cancer Cell Dormancy: An Epigenetic Perspective.International journal of molecular sciences · 2025
    Review
  8. Review
  9. Article
  10. Review
  11. Article
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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

25 authors at 4 institutions in 1 country.

Wazim Mohammed Ismail *Division of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-1782-7296
Amelia Mazzone *Division of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-6236-6962
Flavia G GhiraldiniDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jagneet KaurDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Manvir BainsDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Amik MunankarmyDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-7572-1169
Monique S BagwellDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-4971-1180
Stephanie L SafgrenDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-5503-7324
John Moore-WeissDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Marina BuciucDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Lynzie ShimpDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Kelsey A LeachDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-0816-5155
Luis F DuarteDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Chandandeep S NagiDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Saul CarcamoDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Chi-Yeh ChungDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dan HassonDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neda DadgarDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-3220-7148
Jian ZhongCenter for Individualized Medicine, Epigenomics program, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-7157-603X
Jeong-Heon LeeDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-4007-9166
Fergus J CouchDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Alexander RevzinDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Tamas OrdogCenter for Individualized Medicine, Epigenomics program, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-3940-7284
Emily BernsteinDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-6533-8326
Alexandre Gaspar-MaiaDivision of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. maia.alexandre@mayo.edu.ORCID 0000-0001-8528-5575
Mayo Clinic · USIcahn School of Medicine at Mount Sinai · USMayo Clinic in Florida · USBaylor College of Medicine · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2005 to 2026
$49.9M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0M
THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4M
Resolving the cancer relevance of predisposition gene mutationsR35CA253187 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2020 to 2026
$5.8M
Deciphering the tumor suppressive functions of macroH2AR01CA154683 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BERNSTEIN, EMILY · 2011 to 2021
$3.9M
COVID and Translational Science supercomputer (CATS)S10OD030463 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2021 to 2021
$2.0M
Big Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0M
A microfluidic cell culture platform for personalizing pancreatic cancer therapiesR21CA236612 · NCI · MAYO CLINIC ROCHESTER · PI REVZIN, ALEXANDER · 2020 to 2021
$582k
ASSEMBLY OF VIRUSES, MEMBRANES, AND TISSUER01CA015468 · NCI · BRANDEIS UNIVERSITY · PI CASPAR, DONALD L · 1985 to 1988
–
NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA196521NCI NIH HHS P50 CA116201NCI NIH HHS P50 CA136393NCI NIH HHS R01 CA015468NCI NIH HHS R01 CA154683NCI NIH HHS R21 CA236612NCI NIH HHS R35 CA253187NIH HHS S10 OD026880NIH HHS S10 OD030463
6 · The paper itself

Abstract

Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined 'macro-Bound Enhancers', that modulate enhancer activity. We find macroH2A variants localized at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at inactive enhancers to maintain cell identity. In following, reactivation of macro-bound enhancers is associated with oncogenic programs in breast cancer and their repressive role is correlated with the activity of macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Finally, through single cell epigenomic profiling of normal mammary stem cells derived from mice, we show that macroH2A deficiency facilitates increased activity of transcription factors associated with stem cell activity.

Indexed as

Nuclear ProteinsTranscription FactorsAnimalsCellular ReprogrammingChromatinEnhancer Elements, GeneticHistonesMiceChromatinHistonesmacroH2A histoneNuclear ProteinsTranscription Factors

Identifiers

PMID36823213
PMCPMC9950461
OpenAlexW4321614086

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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.