CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
22 09 2020
Historique:
pubmed: 5 9 2020
medline: 18 11 2020
entrez: 5 9 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32883883
pii: 2003228117
doi: 10.1073/pnas.2003228117
pmc: PMC7519295
doi:

Substances chimiques

Chd7 protein, mouse 0
Core Binding Factor Alpha 2 Subunit 0
DNA-Binding Proteins 0
Runx1 protein, mouse 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

23626-23635

Subventions

Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL100405
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144780
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL091724
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK049216
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA076931
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL032262
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK092760
Pays : United States
Organisme : NIDDK NIH HHS
ID : RC2 DK120535
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL089969
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007439
Pays : United States
Organisme : NIH HHS
ID : R24 OD017870
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228135
Pays : United States
Organisme : Cancer Research UK
ID : C1163/A12765
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL095675
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK127738
Pays : United States
Organisme : Wellcome Trust
ID : 097922/Z/11/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : P01 HL131477
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL133828
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG002668
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK053298
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA148963
Pays : United States

Commentaires et corrections

Type : ErratumIn

Déclaration de conflit d'intérêts

Competing interest statement: L.I.Z. is founder and stockholder of Fate, Scholar Rock, and Camp4 therapeutics and a scientific advisor for Stemgent.

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Auteurs

Jingmei Hsu (J)

Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104.
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104.

Hsuan-Ting Huang (HT)

Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Chung-Tsai Lee (CT)

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104.

Avik Choudhuri (A)

Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138.

Nicola K Wilson (NK)

Cambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.

Brian J Abraham (BJ)

Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.

Victoria Moignard (V)

Cambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.

Iwo Kucinski (I)

Cambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.

Shuqian Yu (S)

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.

R Katherine Hyde (RK)

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.

Joanna Tober (J)

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104.

Xiongwei Cai (X)

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104.

Yan Li (Y)

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104.

Yalin Guo (Y)

Department of Microbiology and Immunology, Geisel School of Medicine, Lebanon, NH 03756.

Song Yang (S)

Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Michael Superdock (M)

Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Eirini Trompouki (E)

Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Fernando J Calero-Nieto (FJ)

Cambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.

Alireza Ghamari (A)

Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Jing Jiang (J)

Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA 19104.

Peng Gao (P)

Division of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.

Long Gao (L)

Division of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.

Vy Nguyen (V)

Stem 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 Robertson (AL)

Stem 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 Durand (EM)

Stem 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 Kathrein (KL)

Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Iannis Aifantis (I)

Department of Pathology and Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016.

Scott A Gerber (SA)

Department of Genetics, Geisel School of Medicine, Lebanon, NH 03756.

Wei Tong (W)

Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA 19104.

Kai Tan (K)

Division of Oncology and Center for Childhood Cancer Research, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Alan B Cantor (AB)

Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

Yi Zhou (Y)

Stem Cell Program and Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.

P Paul Liu (PP)

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.

Richard A Young (RA)

Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.

Berthold Göttgens (B)

Cambridge Institute for Medical Research, Department of Haematology, Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom CB2 OXY.

Nancy A Speck (NA)

Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104; nancyas@upenn.edu zon@enders.tch.harvard.edu.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104.

Leonard I Zon (LI)

Stem 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.
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138.

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