PUBLICATION

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

Authors
Hsu, J., Huang, H.T., Lee, C.T., Choudhuri, A., Wilson, N.K., Abraham, B.J., Moignard, V., Kucinski, I., Yu, S., Hyde, R.K., Tober, J., Cai, X., Li, Y., Guo, Y., Yang, S., Superdock, M., Trompouki, E., Calero-Nieto, F.J., Ghamari, A., Jiang, J., Gao, P., Gao, L., Nguyen, V., Robertson, A.L., Durand, E.M., Kathrein, K.L., Aifantis, I., Gerber, S.A., Tong, W., Tan, K., Cantor, A.B., Zhou, Y., Liu, P.P., Young, R.A., Göttgens, B., Speck, N.A., Zon, L.I.
ID
ZDB-PUB-200905-4
Date
2020
Source
Proceedings of the National Academy of Sciences of the United States of America   117(38): 23626-23635 (Journal)
Registered Authors
Robertson, Anne, Trompouki, Eirini, Zon, Leonard I.
Keywords
CHD7, RUNX1, hematopoiesis
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Line
  • Core Binding Factor Alpha 2 Subunit*/chemistry
  • Core Binding Factor Alpha 2 Subunit*/genetics
  • Core Binding Factor Alpha 2 Subunit*/metabolism
  • DNA-Binding Proteins*/chemistry
  • DNA-Binding Proteins*/genetics
  • DNA-Binding Proteins*/metabolism
  • Female
  • Hematopoiesis*
  • Hematopoietic Stem Cells
  • Humans
  • Male
  • Mice
  • Spleen/cytology
  • Zebrafish
PubMed
32883883 Full text @ Proc. Natl. Acad. Sci. USA
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes
Correction: https://www.pnas.org/doi/full/10.1073/pnas.2114827118 Corrects Article: https://www.pnas.org/doi/10.1073/pnas.2003228117