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.
Highlights
The differentiation of preadipocytes into adipocytes is modulated by diverse transcription factors that coordinate the expression of genes responsible for determining the mature fat-cell feature [1, 2]
To determine whether the expression of JMJD2D is correlated with that of peroxisome proliferator-activated receptor γ (PPARγ) and C/ EBPα during adipogenesis, we examined the expressions of JMJD2D, PPARγ, and CCAAT/enhancer-binding protein α (C/EBPα) at certain periods after induction of adipogenesis
Since we demonstrated in the present study that JMJD2B removes H3K9me3 on the promoters of PPARγ and C/EBPα, we investigated whether this JMJD2B-mediated removal of H3K9me3 favors the occupancy of H3K4me3 on the promoters
Summary
The differentiation of preadipocytes into adipocytes (adipogenesis) is modulated by diverse transcription factors that coordinate the expression of genes responsible for determining the mature fat-cell feature [1, 2]. At the early stage of adipogenesis, the transcription factors, including the CCAAT/enhancer-binding protein (C/EBP) β/δ, glucocorticoid receptor (GR), Kruppel-like factor 5 (KLF5), cAMP response element-binding protein (CREB), early growth response protein 2 (EGR2 or Krox20), and sterol regulatory element-binding protein 1c. Epigenetic Regulation of PPARγ and C/EBPα Expression by JMJD2B
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