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CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

Authors: 
Hsu J, Huang HT, Lee CT, Choudhuri A, Wilson NK, Abraham BJ, Moignard V, Kucinski I, Yu S, Hyde RK, Tober J, Cai X, Li Y, Guo Y, Yang S, Superdock M, Trompouki E, Calero-Nieto FJ, Ghamari A, Jiang J, Gao P, Gao L, Nguyen V, Robertson AL, Durand EM, Kathrein KL, Aifantis I, Gerber SA, Tong W, Tan K, Cantor AB, Zhou Y, Liu PP, Young RA, Göttgens B, Speck NA, Zon LI
Citation: 
Proc Natl Acad Sci U S A. 2020 Sep 3:202003228. doi: 10.1073/pnas.2003228117. Online ahead of print
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.
Epub: 
Yes
Organism or Cell Type: 
zebrafish
Delivery Method: 
microinjection