English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

MPS-Authors
/persons/resource/persons241707

Trompouki,  Eirini
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource
Fulltext (public)

Hsu et al..pdf
(Publisher version), 4MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Hsu, J., Huang, H.-T., Lee, C.-T., Choudhuri, A., Wilson, N. K., Abraham, B. J., et al. (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, 23626-23635.


Cite as: http://hdl.handle.net/21.11116/0000-0007-DCCA-E
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.