ArticleProceedings of the National Academy of Sciences of the United States of America2020
CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.
Erratum issuedOpen access · bronzeAbstract read
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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17citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- The Runx1-Gata2 axis: epigenetic architecture of lineage fate.Molecular biology reports · 2026Review
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2.Leukemia · 2026Article
- Nap1L4a Cooperates with Scl/Klf1 to Recruit H2A.Z in Mediating Interactions Among Cis-Regulatory Elements and Transcription Required for Primitive Erythropoiesis in Zebrafish.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel cardiomyopathy phenotype linked to a CHD7 missense variant.Scientific reports · 2025Article
- Chromatin remodeling in tissue stem cell fate determination.Cell regeneration (London, England) · 2024Review
- Neurodevelopmental functions of CHD8: new insights and questions.Biochemical Society transactions · 2024Review
- Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature.Blood advances · 2023Article
- A critical role of RUNX1 in governing megakaryocyte-primed hematopoietic stem cell differentiation.Blood advances · 2023Article
- Improving the differentiation potential of pluripotent stem cells by optimizing culture conditions.Scientific reports · 2022Article
- Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells.Biomaterials · 2022Article
- Sentinels of chromatin: chromodomain helicase DNA-binding proteins in development and disease.Genes & development · 2021Review
- Article
- [The Roles of RUNX1 in the Proliferation and Osteogenic and Adipogenic Differentiation of Dental Pulp Stem Cells].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci.Nature genetics · 2021Article
- Advances in Chromodomain Helicase DNA-Binding (CHD) Proteins Regulating Stem Cell Differentiation and Human Diseases.Frontiers in cell and developmental biology · 2021Review
- Chromatin Imbalance as the Vertex Between Fetal Valproate Syndrome and Chromatinopathies.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
37 authors at 9 institutions in 2 countries.
Jingmei HsuDivision of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104.
Hsuan-Ting HuangStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.ORCID 0000-0003-0383-8020
Chung-Tsai LeeAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0003-0676-1380
Avik ChoudhuriDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138.
Nicola K WilsonCambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.ORCID 0000-0003-0865-7333
Brian J AbrahamWhitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
Victoria MoignardCambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.
Iwo KucinskiCambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.
Shuqian YuAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
R Katherine HydeNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
Joanna ToberAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
Xiongwei CaiAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-9990-2615
Yan LiAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0003-4813-5783
Yalin GuoDepartment of Microbiology and Immunology, Geisel School of Medicine, Lebanon, NH 03756.ORCID 0000-0002-7676-140X
Song YangStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Michael SuperdockStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Eirini TrompoukiStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-7242-8810
Fernando J Calero-NietoCambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.
Alireza GhamariDivision of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Jing JiangDivision of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Peng GaoDivision of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Long GaoDivision of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Vy NguyenStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Anne L RobertsonStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Ellen M DurandStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Katie L KathreinStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Iannis AifantisDepartment of Pathology and Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016.
Scott A GerberDepartment of Genetics, Geisel School of Medicine, Lebanon, NH 03756.
Wei TongDivision of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Kai TanDivision of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.ORCID 0000-0002-9104-5567
Alan B CantorDivision of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Yi ZhouStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.ORCID 0000-0003-0935-1635
P Paul LiuNational Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
Richard A YoungWhitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
Berthold GöttgensCambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.ORCID 0000-0001-6302-5705
Nancy A SpeckAbramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104; nancyas@upenn.edu zon@enders.tch.harvard.edu.ORCID 0000-0002-1893-582X
Leonard I ZonStem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; nancyas@upenn.edu zon@enders.tch.harvard.edu.ORCID 0000-0003-0860-926X
Boston Children's Hospital · USCancer Research Institute · USChildren's Hospital of Philadelphia · USWellcome/MRC Cambridge Stem Cell Institute · GBDartmouth College · USNational Institutes of Health · USWhitehead Institute for Biomedical Research · USHarvard University · USNew York University · US
Funding
TRANSCRIPTION FACTOR GATA-1 IN TERMINAL ERYTHROID DEVELOPMENTP01HL032262 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1985 to 2021
$38.9MTranscriptional and epigenetic heterogeneity of stem/progenitor cellsP01HL131477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI DANIEL G TENEN · 2017 to 2026
$24.6MTranscriptional Regulatory Networks in Living CellsR01HG002668 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI YOUNG, RICHARD · 2003 to 2016
$17.9MHEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1MPhysician Scientist Training in Clinical OncologyK12CA076931 · NCI · UNIVERSITY OF PENNSYLVANIA · PI STEPHEN Patrick HUNGER, LYNN M. SCHUCHTER · 1997 to 2026
$16.5MCORE--ZEBRAFISHP30DK049216 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI ZHOU, YI · 1999 to 2015
$14.3MCustomized stem cells for clinical application in blood disordersR24DK092760 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2011 to 2018
$10.7MBiochemistry of Leukemia Virus Core-Binding FactorR01HL091724 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SPECK, NANCY · 2008 to 2024
$8.3MMolecular Circuits in the Hematopoietic Stem Cell NicheRC2DK120535 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2020 to 2024
$8.2MExpansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1MA Community Zebrafish Resource for Modeling GWAS BiologyR24OD017870 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI GOESSLING, WOLFRAM, MACRAE, CALUM A. · 2014 to 2021
$6.3MLnk Regulatory Functions in Hematopoietic Stem CellsR01HL095675 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI TONG, WEI · 2009 to 2021
$5.6MCancer Research UK 12765Cancer Research UK 21762Cancer Research UK C1163/A12765Howard Hughes Medical InstituteMedical Research Council MC_PC_12009NCI NIH HHS K12 CA076931NCI NIH HHS R00 CA148963NCI NIH HHS R01 CA228135NHGRI NIH HHS R01 HG002668NHLBI NIH HHS P01 HL032262NHLBI NIH HHS P01 HL131477NHLBI NIH HHS R01 HL089969NHLBI NIH HHS R01 HL091724NHLBI NIH HHS R01 HL095675NHLBI NIH HHS R01 HL133828NHLBI NIH HHS R01 HL144780NHLBI NIH HHS T32 HL007439NHLBI NIH HHS U01 HL100405NIDDK NIH HHS P30 DK049216NIDDK NIH HHS R01 DK053298NIDDK NIH HHS R01 DK127738NIDDK NIH HHS R24 DK092760NIDDK NIH HHS RC2 DK120535NIH HHS R24 OD017870Wellcome TrustWellcome Trust 097922/Z/11/Z
Abstract
Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
Indexed as
Core Binding Factor Alpha 2 SubunitDNA-Binding ProteinsHematopoiesisAnimalsCell DifferentiationCell LineFemaleHematopoietic Stem CellsHumansMaleMiceSpleenZebrafishChd7 protein, mouseCore Binding Factor Alpha 2 SubunitDNA-Binding ProteinsRunx1 protein, mouseCHD7hematopoiesisRUNX1
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