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

Accepted version
Peer-reviewed

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Authors

Hsu, Jingmei 
Choudhuri, Avik 

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.

Description

Keywords

CHD7, RUNX1, hematopoiesis, Animals, Cell Differentiation, Cell Line, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Female, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Mice, Spleen, Zebrafish

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

117

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Leukaemia & Lymphoma Research (12029)
Cancer Research UK (21762)
Leukemia & Lymphoma Society (7001-12)
Wellcome Trust (097922/Z/11/Z)
Medical Research Council (MC_PC_12009)
Cancer Research Uk (None)
Bloodwise, CRUK, MRC, Wellcome Trust, NIH, Leukemia and Lymphoma Society