Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

Table 3

Epigenetic regulation of adipogenic differentiation of mesenchymal stem cells.

Epigenetic regulation	Target	Finding	Reference
DNA methylation	PPARγ2, lep, fabp4, lpl	Promoters for these 4 adipogenic genes are hypomethylated in ASCs	Noer et al. [150]
DNA methylation	PPARγ	Expression of PPARγ is regulated by promoter DNA methylation. Promoter methylation corresponds to a decreased expression of PPARγ and decreased adipogenic differentiation	Fujiki et al. [151]
DNA methylation	Glut4	Promoter DNA demethylation occurs as cells undergo adipogenic differentiation	Yokomori et al. [152]
DNA methylation	Lep	The Lep promoter region is highly methylated in preadipocytes but is unmethylated in terminally differentiated adipocytes	Melzner et al. [234]
DNA methylation	Agouti	Genistein-mediated DNA hypermethylation of a retrotransposon upstream of Agouti is associated with decreased obesity	Dolinoy et al. [153]
Histone modification	ApM1	H3 hyperacetylation and H3K4me3 at the apM1 promoter region correlate with early adipogenic differentiation. Inhibition of H3K4 methylation results in decreased apM1 expression and decreased adipogenesis	Musri et al. [154]
Histone modification	Multiple gene promoters	Downregulation of HDACs is required for adipogenic differentiation	Yoo et al. [155]
Histone modification	PPARγ gene targets	Unphosphorylated RB recruits HDAC3 to promoters of PPARγ gene targets, which decreases adipogenic differentiation. Inhibition of HDAC3 activity results in PPARγ activation, and subsequent adipogenesis	Fajas et al. [156]

PPARγ: peroxisome proliferator-activated receptor-gamma; lep: leptin; fabp4: fatty acid-binding protein 4; lpl: lipoprotein lipase; ASC: adipose-derived stem cell; Glut4: glucose transporter type 4; ApM1: adiponectin; H3K4me3: Trimethylation of lysine 4 on histone 3; HDAC: histone deacetylase; RB: retinoblastoma.