Targeted erasure of DNA methylation by TET3 drives adipogenic reprogramming and differentiation

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Title
Targeted erasure of DNA methylation by TET3 drives adipogenic reprogramming and differentiation
Author(s)
J Park; D H Lee; S Ham; J Oh; Jung Ran Noh; Y K Lee; Y J Park; G Lee; S M Han; J S Han; Y Y Kim; Y G Jeon; H Nahmgoong; K C Shin; S M Kim; S H Choi; Chul-Ho Lee; J Park; T Y Roh; S Kim; J B Kim
Bibliographic Citation
Nature Metabolism, vol. 4, no. 7, pp. 918-931
Publication Year
2022
Abstract
DNA methylation is a crucial epigenetic modification in the establishment of cell-type-specific characteristics. However, how DNA methylation is selectively reprogrammed at adipocyte-specific loci during adipogenesis remains unclear. Here, we show that the transcription factor, C/EBPδ, and the DNA methylation eraser, TET3, cooperatively control adipocyte differentiation. We perform whole-genome bisulfite sequencing to explore the dynamics and regulatory mechanisms of DNA methylation in adipocyte differentiation. During adipogenesis, DNA methylation selectively decreases at adipocyte-specific loci carrying the C/EBP binding motif, which correlates with the activity of adipogenic promoters and enhancers. Mechanistically, we find that C/EBPδ recruits a DNA methylation eraser, TET3, to catalyse DNA demethylation at the C/EBP binding motif and stimulate the expression of key adipogenic genes. Ectopic expression of TET3 potentiates in vitro and in vivo adipocyte differentiation and recovers downregulated adipogenic potential, which is observed in aged mice and humans. Taken together, our study highlights how targeted reprogramming of DNA methylation through cooperative action of the transcription factor C/EBPδ, and the DNA methylation eraser TET3, controls adipocyte differentiation.
ISSN
2522-5812
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s42255-022-00597-7
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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