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. CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation. Proc Natl Acad Sci U S A. 2020 Sep 03.

Citation

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. 2020. CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation. Proceedings of the National Academy of Sciences of the United States of America. 117(38):23626-23635. Pubmed: 32883883 DOI: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.

Related Faculty

Leonard Zon, M.D.

Zon Lab

The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.