CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation

Jingmei Hsu, Hsuan Ting Huang, Chung Tsai Lee, Avik Choudhuri, Nicola K. Wilson, Brian J. Abraham, Victoria Moignard, Iwo Kucinski, Shuqian Yu, R. Katherine Hyde, Joanna Tober, Xiongwei Cai, Yan Li, Yalin Guo, Song Yang, Michael Superdock, Eirini Trompouki, Fernando J. Calero-Nieto, Ghamari Alireza, Jing JiangPeng Gao, Long Gao, Vy Nguyen, Anne L. Robertson, Ellen M. Durand, Katie L. Kathrein, Iannis Aifantis, Scott A. Gerber, Wei Tong, Kai Tan, Alan B. Cantor, Yi Zhou, P. Paul Liu, Richard A. Young, Berthold Göttgens, Nancy A. Speck, Leonard I. Zon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)23626-23635
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number38
DOIs
StatePublished - Sep 22 2020
Externally publishedYes

Keywords

  • CHD7
  • Hematopoiesis
  • RUNX1

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation'. Together they form a unique fingerprint.

Cite this