PUBLICATION
Tet Proteins Regulate Neutrophil Granulation in Zebrafish through Demethylation of socs3b mRNA
- Authors
- Banks, K.M., Lan, Y., Evans, T.
- ID
- ZDB-PUB-210114-20
- Date
- 2021
- Source
- Cell Reports 34: 108632 (Journal)
- Registered Authors
- Evans, Todd
- Keywords
- cytokine, epitranscriptomics, mRNA stability, methylation, myelopoiesis
- Datasets
- GEO:GSE162435, GEO:GSE162433, GEO:GSE162431
- MeSH Terms
-
- Animals
- Demethylation
- Dioxygenases/metabolism*
- Granulation Tissue
- Neutrophils/metabolism*
- RNA/metabolism*
- Suppressor of Cytokine Signaling 3 Protein/metabolism*
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 33440144 Full text @ Cell Rep.
Citation
Banks, K.M., Lan, Y., Evans, T. (2021) Tet Proteins Regulate Neutrophil Granulation in Zebrafish through Demethylation of socs3b mRNA. Cell Reports. 34:108632.
Abstract
Tet proteins (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC), initiating the process of active demethylation to regulate gene expression. Demethylation has been investigated primarily in the context of DNA, but recently Tet enzymes have also been shown to mediate demethylation of 5mC in RNA as an additional level of epitranscriptomic regulation. We analyzed compound tet2/3 mutant zebrafish and discovered a role for Tet enzymes in the maturation of primitive and definitive neutrophils during granulation. Transcript profiling showed dysregulation of cytokine signaling in tet mutant neutrophils, including upregulation of socs3b. We show that Tet normally demethylates socs3b mRNA during granulation, thereby destabilizing the transcript, leading to its downregulation. Failure of this process leads to accumulation of socs3b mRNA and repression of cytokine signaling at this crucial step of neutrophil maturation. This study provides further evidence for Tets as epitranscriptomic regulatory enzymes and implicates Tet2/3 in regulation of neutrophil maturation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping