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5mC profiling characterized TET2 as an anti-adipogenic demethylase.
- Source :
-
Gene . Apr2020, Vol. 733, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- • TET2 is the most regulated 5mC demethylase during 3 T3-L1 differentiation. • TET2 is identified as an anti-adipogenic demethylase by loss-of function and gain-of function assays. • TET2 inhibits lipid accumulation by promoter demethylation of Adrb3. • Vitamin C was found to decrease 5mC level and repress lipid production. To explore its roles in adipogenesis, the levels of genomic 5mC methylation were examined across the adipocyte differentiation of 3 T3-L1 cells. This led to the identification of an up-regulating 5mC profile during the process. To further explore the regulation, gene expression assay was performed with a set of 5mC metabolic enzymes. Among them, TET2 was found to be the most regulated 5mC demethylase, in addition to a well-investigated 5mC methylase DNMT1. In the process, the expression of Tet2 increased for over 16-fold, suggesting its implications in the differentiation. Therefore, loss-of-function and gain-of-function assays were performed with Tet2. It was found that in relative to the differentiation of wild-type cells, knockdown of Tet2 expression led to greatly enhanced differentiation process, while over-expression of the gene resulted in repressed differentiation. Pathway study found that during the differentiation, TET2 demethylates Adrb3 promoter to up-regulate its expression. This led to enhanced lipolysis and decreased lipid production. To the upstream pathway, vitamin C treatment was found to enhance the activity of TETs, decrease 5mC levels and repress lipid production. Taken together, TET2 was characterized as an anti-adipogenic demethylase in adipocyte differentiation of 3 T3-L1 cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03781119
- Volume :
- 733
- Database :
- Academic Search Index
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 141730580
- Full Text :
- https://doi.org/10.1016/j.gene.2019.144265