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성균관대학교 약학대학

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Mol. Cell, Available online 14 April 2016, DOI: http://dx.doi.org/10.1016/j.molcel.2016.03.011 S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

Abstract

Sang Ah Yi,¹ Sung Hee Um,^2,3 Jaecheol Lee,⁴ Ji Hee Yoo,¹ So Young Bang,¹ Eun Kyung Park,¹ Min Gyu Lee,¹ Ki Hong Nam,¹ Ye Ji Jeon,¹ Jong Woo Park,¹ Jueng Soo You,⁵ Sang-Jin Lee,⁶ Gyu-Un Bae,⁶ Jong Won Rhie,⁷ Sara C. Kozma, ^8,9 George Thomas, ^8,9,10,* and Jeung-Whan Han ^1,*

¹Research Center for Epigenome Regulation, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
²Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea
³Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Seoul 06351, Republic of Korea
⁴Division of Cardiology, Department of Medicine, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305-5454, USA
⁵Department of Biochemistry, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea
⁶Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Republic of Korea
⁷Department of Plastic Surgery, College of Medicine, Catholic University of Korea, Seoul 06591, Republic of Korea
⁸Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
⁹Laboratory of Cancer Metabolism, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, Spain
¹⁰Unitat de Bioquímica, Dep. Ciències Fisiològiques II, Facultat de Medicina, Campus Universitari de Bellvitge - IDIBELL, Universitat de Barcelona, 08908 L’Hospitalet de Llobregat, Catalunya, Barcelona, Spain

*Correspondence: George Thomas, Jeung-Whan Han

SUMMARY
S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

논문정보

형식Research article
게재일2016년 04월 (BRIC 등록일 2016-04-19)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생화학

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