The H3K27 demethylase, Utx, regulates adipogenesis in a differentiation stage-dependent manner.
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes. Utx-deficient mESCs showed diminished potential to differentiate to adipocytes compared to that of controls. In contrast, Utx-deficient preadipocytes showed enhanced differentiation to adipocytes. Microarray analyses indicated that the β-catenin/c-Myc signaling pathway was differentially regulated in Utx-deficient cells during adipocyte differentiation. Therefore, our data suggest that Utx governs adipogenesis by regulating c-Myc in a differentiation stage-specific manner and that targeting the Utx signaling pathway could be beneficial for the treatment of obesity, diabetes, and congenital utx-deficiency disorders.
Department of Biochemistry, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
Kazushige
K
Ota
Princess Margaret Cancer Centre, Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Canada.
Kit I
KI
Tong
Princess Margaret Cancer Centre, Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Canada.
Kouichiro
K
Goto
Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
Shuta
S
Tomida
Department of Biochemistry, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
Akiyoshi
A
Komuro
Department of Cardiac Surgery, Cardiovascular Research Center, University of Michigan, Ann Arbor, Michigan, United States of America.
Zhong
Z
Wang
Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.
Kazuto
K
Nishio
Department of Biochemistry, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan.|Princess Margaret Cancer Centre, Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Canada.|Anti-Aging Center, Kindai University, Higashi Osaka, Osaka, Japan.
Hitoshi
H
Okada
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D056466:Histone Demethylases / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D056466:Histone Demethylases; C111778:Utx protein, mouse