title: Histone H3K9 Demethylase JMJD2B Activates Adipogenesis by Regulating H3K9 Methylation on PPARγ and C/EBPα during Adipogenesis.
abstract: Previous studies have shown that tri- or di-methylation of histone H3 at lysine 9 (H3K9me3/me2) on the promoter of the peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) contribute to the repression of PPARγ and C/EBPα and inhibition of adipogenesis in 3T3-L1 preadipocytes. The balance of histone methylation is regulated by histone methyltransferases and demethylases. However, it is poorly understood which demethylases are responsible for removing H3K9me3/me2 on the promoter of PPARγ and C/EBPα. JMJD2B is a H3K9me3/me2 demethylase that was previously shown to activate adipogenesis by promoting mitotic clonal expansion. Nevertheless, it remains unclear whether JMJD2B plays a role in the regulation of adipogenesis by removing H3K9me3/me2 on the promoter of PPARγ and C/EBPα and subsequently activating PPARγ and C/EBPα expression. Here, we showed that JMJD2B decreased H3K9me3/me2 on the promoter of PPARγ and C/EBPα, which in turn stimulated the expression of PPARγ and C/EBPα. JMJD2B knockdown using siRNA in 3T3-L1 preadipocytes repressed the expression of PPARγ and C/EBPα, resulting in inhibition of adipogenesis. This was accompanied by increased enrichment of H3K9me3/me2 on the promoter of PPARγ and C/EBPα. In contrast, overexpression of JMJD2B increased the expression of PPARγ and C/EBPα, which was accompanied by decreased enrichment of H3K9me3/me2 on the promoter and activated adipogenesis. Together, these results indicate that JMJD2B regulates PPARγ and C/EBPα during adipogenesis.
authors.affiliation: School of Korean Medicine, Pusan National University, 49 Busandaehak-ro, Mulguem-eup, Yangsan-si, Gyeongnam, South Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Jang
authors.affiliation: School of Korean Medicine, Pusan National University, 49 Busandaehak-ro, Mulguem-eup, Yangsan-si, Gyeongnam, South Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: School of Korean Medicine, Pusan National University, 49 Busandaehak-ro, Mulguem-eup, Yangsan-si, Gyeongnam, South Korea.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D047495:PPAR gamma / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D006657:Histones; D047495:PPAR gamma; D056484:Jumonji Domain-Containing Histone Demethylases; C511781:Kdm4b protein, mouse