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박지영

Park, Jiyoung
Molecular Metabolism Lab.
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Targeted erasure of DNA methylation by TET3 drives adipogenic reprogramming and differentiation

Author(s)
Park, JeuLee, Do HoonHam, SeokjinOh, JiyoungNoh, Jung-RanLee, Yun KyungPark, Yoon JeongLee, GungHan, Sang MunHan, Ji SeulKim, Ye YoungJeon, Yong GeunNahmgoong, HanShin, Kyung CheulKim, Sung MinChoi, Sung HeeLee, Chul-HoPark, JiyoungRoh, Tae YoungKim, SunKim, Jae Bum
Issued Date
2022-07
DOI
10.1038/s42255-022-00597-7
URI
https://scholarworks.unist.ac.kr/handle/201301/58968
Citation
NATURE METABOLISM, v.4, no.7, pp.918 - 931
Abstract
Park et al. shed light on the dynamics of DNA demethylation during adipocyte differentiation, which is shown to be regulated by the transcription factor C/EBP delta and the DNA methylation eraser TET3. 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/EBP delta, 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/EBP delta 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/EBP delta, and the DNA methylation eraser TET3, controls adipocyte differentiation.
Publisher
NATURE PORTFOLIO
ISSN
2522-5812
Keyword
ADIPOSE-TISSUEFATDEMETHYLATIONESTABLISHMENTHOTSPOTSLINEAGEDNMT3AROLES

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