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

Autor: Park J; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Lee DH; Bioinformatics Institute, Seoul National University, Seoul, South Korea., Ham S; Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea., Oh J; Department of Biological Sciences, College of Information and Bioengineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea., Noh JR; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon, South Korea., Lee YK; Internal Medicine, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seoul, South Korea., Park YJ; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Lee G; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Han SM; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Han JS; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Kim YY; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Jeon YG; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Nahmgoong H; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Shin KC; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Kim SM; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea., Choi SH; Internal Medicine, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Seoul, South Korea., Lee CH; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon, South Korea., Park J; Department of Biological Sciences, College of Information and Bioengineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea., Roh TY; Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea., Kim S; Department of Computer Science and Engineering, Institute of Engineering Research, Seoul National University, Seoul, South Korea., Kim JB; Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea. jaebkim@snu.ac.kr.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2022 Jul; Vol. 4 (7), pp. 918-931. Date of Electronic Publication: 2022 Jul 04.
DOI: 10.1038/s42255-022-00597-7
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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