Tet Proteins Regulate Neutrophil Granulation in Zebrafish through Demethylation of socs3b mRNA.

TitleTet Proteins Regulate Neutrophil Granulation in Zebrafish through Demethylation of socs3b mRNA.
Publication TypeJournal Article
Year of Publication2021
AuthorsBanks, KM, Lan, Y, Evans, T
JournalCell Rep
Volume34
Issue2
Pagination108632
Date Published2021 Jan 12
ISSN2211-1247
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.

DOI10.1016/j.celrep.2020.108632
Alternate JournalCell Rep
PubMed ID33440144