PUBLICATION
The scaffolding function of LSD1/KDM1A reinforces a negative feedback loop to repress stem cell gene expression during primitive hematopoiesis
- Authors
- Casey, M.J., Call, A.M., Thorpe, A.V., Jette, C.A., Engel, M.E., Stewart, R.A.
- ID
- ZDB-PUB-230104-1
- Date
- 2022
- Source
- iScience 26: 105737105737 (Journal)
- Registered Authors
- Jette, Cicely A., Stewart, Rodney A.
- Keywords
- Cell biology, Molecular biology, Molecular interaction, Stem cells research
- Datasets
- GEO:GSE198476
- MeSH Terms
- none
- PubMed
- 36594016 Full text @ iScience
Citation
Casey, M.J., Call, A.M., Thorpe, A.V., Jette, C.A., Engel, M.E., Stewart, R.A. (2022) The scaffolding function of LSD1/KDM1A reinforces a negative feedback loop to repress stem cell gene expression during primitive hematopoiesis. iScience. 26:105737105737.
Abstract
Lsd1/Kdm1a functions both as a histone demethylase enzyme and as a scaffold for assembling chromatin modifier and transcription factor complexes to regulate gene expression. The relative contributions of Lsd1's demethylase and scaffolding functions during embryogenesis are not known. Here, we analyze two independent zebrafish lsd1/kdm1a mutant lines and show Lsd1 is required to repress primitive hematopoietic stem cell gene expression. Lsd1 rescue constructs containing point mutations that selectively abrogate its demethylase or scaffolding capacity demonstrate the scaffolding function of Lsd1, not its demethylase activity, is required for repression of gene expression in vivo. Lsd1's SNAG-binding domain mediates its scaffolding function and reinforces a negative feedback loop to repress the expression of SNAG-domain-containing genes during embryogenesis, including gfi1 and snai1/2. Our findings reveal a model in which the SNAG-binding and scaffolding function of Lsd1, and its associated negative feedback loop, provide transient and reversible regulation of gene expression during hematopoietic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping