CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation
- 3 September 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (38), 23626-23635
- https://doi.org/10.1073/pnas.2003228117
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.Funding Information
- HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL089969)
- HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL091724)
- HHS | NIH | National Heart, Lung, and Blood Institute (U01HL100405)
- HHS | NIH | National Heart, Lung, and Blood Institute (R01 HL04880)
- HHS | NIH | National Heart, Lung, and Blood Institute (PPG-P015PO1HL32262-32)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (5P30 DK49216)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (5R01 DK53298)
- HHS | NIH | National Heart, Lung, and Blood Institute (5U01 HL10001-05)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R24 DK092760)
- HHS | NIH | National Human Genome Research Institute (HG002668)
- HHS | NIH | National Cancer Institute (NIH4R00CA148963)
- Bloodwise (Bloodwise grant 12029)
- Leukemia and Lymphoma Society (Leukemia and Lymphoma Society grant 7001-12)
- Cancer Research UK (CRUK grant C1163/A12765)
- Wellcome Trust and MRC to the Wellcome Trust and MRC Cambridge Stem Cell Institute (097922/Z/11/Z)
- HHS | NIH | National Heart, Lung, and Blood Institute (5-T32-HL-007439-34)
- HHS | NIH | National Cancer Institute (K12CA076931)
- New York State Stem Cell Science (C026880)
- Howard Hughes Medical Institute (No number)
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