| Literature DB >> 32883883 |
Jingmei Hsu1,2,3, Hsuan-Ting Huang4, Chung-Tsai Lee2,3, Avik Choudhuri5, Nicola K Wilson6, Brian J Abraham7, Victoria Moignard6, Iwo Kucinski6, Shuqian Yu2, R Katherine Hyde8, Joanna Tober2,3, Xiongwei Cai2,3, Yan Li2,3, Yalin Guo9, Song Yang4, Michael Superdock4, Eirini Trompouki4, Fernando J Calero-Nieto6, Alireza Ghamari10, Jing Jiang11, Peng Gao12, Long Gao12, Vy Nguyen4, Anne L Robertson4, Ellen M Durand4, Katie L Kathrein4, Iannis Aifantis13, Scott A Gerber14, Wei Tong11, Kai Tan12,15, Alan B Cantor10, Yi Zhou4, P Paul Liu8, Richard A Young7, Berthold Göttgens6, Nancy A Speck16,3, Leonard I Zon17,5.
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.Entities:
Keywords: CHD7; RUNX1; hematopoiesis
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Year: 2020 PMID： 32883883 PMCID： PMC7519295 DOI： 10.1073/pnas.2003228117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779