Evidence map›Paper›PMID 27570068›Full record

ArticleCell stem cell2016

MED12 Regulates HSC-Specific Enhancers Independently of Mediator Kinase Activity to Control Hematopoiesis.

Beatriz Aranda-Orgilles, Ricardo Saldaña-Meyer, Eric Wang, Eirini Trompouki, Anne Fassl, Stephanie Lau, Jasper Mullenders, Pedro P Rocha, Ramya Raviram, María Guillamot and 14 more

Open access · greenAbstract read
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 107 citations in OpenAlex.

  1. Review
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  5. Functional-genomic prioritization identifiesFrontiers in pharmacology · 2026
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  7. UTERINE FIBROIDS.Physiological reviews · 2025
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  9. MED12 dysregulation: insights into cancer and therapeutic resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
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  14. Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.Genetics in medicine : official journal of the American College of Medical Genetics · 2024
    Article
  15. tRNA mNature communications · 2024
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  16. Circular RNAs: a small piece in the heart failure puzzle.Functional & integrative genomics · 2024
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16 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 7 institutions in 2 countries.

Beatriz Aranda-OrgillesDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Ricardo Saldaña-MeyerHoward Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Eric WangDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Eirini TrompoukiDepartment of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Anne FasslDepartment of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Stephanie LauDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Jasper MullendersDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Pedro P RochaDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Ramya RaviramDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
María GuillamotDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
María Sánchez-DíazDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Kun WangDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Clarisse KayembeDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Nan ZhangDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Leonela AmoasiiDepartment of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Avik ChoudhuriStem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
Jane A SkokDepartment of Pathology, NYU School of Medicine, New York, NY 10016, USA.
Markus SchoberThe Ronald O. Perelman Department of Dermatology and Department of Cell Biology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
Danny ReinbergHoward Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Piotr SicinskiDepartment of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Heinrich SchreweDepartment of Developmental Genetics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Aristotelis TsirigosDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA; Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, NY 10016, USA.
Leonard I ZonStem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
Iannis AifantisDepartment of Pathology, Laura & Isaac Perlmutter Cancer Center, and The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA. Electronic address: iannis.aifantis@nyumc.org.
New York University · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterHarvard University · USHoward Hughes Medical Institute · USMax Planck Institute for Molecular Genetics · DEMax Planck Institute of Immunobiology and Epigenetics · DEThe University of Texas Southwestern Medical Center · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Aristotelis Tsirigos · 1985 to 2026
$83.1M
CORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D · 1999 to 2014
$14.9M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Role of TET2 mutations in malignant transformation and acute myeloid leukemiaR01CA173636 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2013 to 2022
$6.3M
Project-002U54DK110805 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ORKIN, STUART H, ZON, LEONARD IRA · 2016 to 2020
$5.9M
EMBRYONIC HEMATOPOIESISR01HL048801 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 1992 to 2016
$5.7M
The role of the SCF/FBW7 ubiquitin ligase complex in hematopiesis and leukemia.R01CA133379 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2009 to 2018
$3.6M
Regulation of hematopoietic stem cell differentiationR01CA105129 · NCI · UNIVERSITY OF CHICAGO · PI AIFANTIS, IANNIS · 2005 to 2014
$2.8M
Long non-coding RNAs in hematopoiesis and blood malignancyR01CA194923 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2015 to 2019
$2.3M
The function of cyclin C in tumorigenesisR01CA190509 · NCI · DANA-FARBER CANCER INST · PI SICINSKI, PETER · 2015 to 2019
$2.3M
Mechanisms of T cell leukemia induction and maintenanceR01CA149655 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2010 to 2015
$2.0M
Genetic Dissection of Acute Myeloid Leukemia.R01CA169784 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2014 to 2018
$1.8M
NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA105129NCI NIH HHS R01 CA133379NCI NIH HHS R01 CA149655NCI NIH HHS R01 CA169784NCI NIH HHS R01 CA173636NCI NIH HHS R01 CA190509NCI NIH HHS R01 CA194923NHLBI NIH HHS R01 HL048801NIDDK NIH HHS P30 DK056465NIDDK NIH HHS U54 DK106829NIDDK NIH HHS U54 DK110805NIGMS NIH HHS K99 GM117302
6 · The paper itself

Abstract

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis.

Indexed as

HematopoiesisAnimalsApoptosisBone MarrowCell SurvivalChromatinEnhancer Elements, GeneticGene DeletionGene Expression ProfilingHematopoietic Stem CellsMediator ComplexMicep300-CBP-Associated Factorp300-CBP Transcription FactorsProtein BindingTranscription FactorsChromatinMed12 protein, mouseMediator Complexp300-CBP-Associated Factorp300-CBP Transcription FactorsTranscription Factors

Identifiers

PMID27570068
PMCPMC5268820
OpenAlexW2513070235

What OpenQuestion holds

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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.