title: Epigenetic regulation of adipocyte differentiation by a Rho guanine nucleotide exchange factor, WGEF.
abstract: Epigenetic regulation, including DNA methylation, plays an important role in several differentiation processes and possibly in adipocyte differentiation. To search for genes that show methylation change during adipogenesis, genome-wide DNA methylation analysis in insulin-induced adipogenesis of 3T3-L1 preadipocyte cells was performed using a method called microarray-based integrated analysis of methylation by isoschizomers (MIAMI). The MIAMI revealed that Hpa II sites of exon 1 in a Rho guanine nucleotide exchange factor 19 (ARHGEF19; WGEF) gene were demethylated during adipocyte differentiation of 3T3-L1 cells. Deletion of the region containing cytosine-guanine (CpG) sites that showed methylation change suppressed transcriptional activity in the reporter assay, indicating that this region regulates WGEF transcription. WGEF expression in 3T3-L1 cells was reduced during adipocyte differentiation, and high-fat diet-induced obese mice also showed lower expression of WGEF gene than control mice in white adipose tissue. Additionally, forced expression of WGEF in 3T3-L1 cells down-regulated the expression of adipogenic marker genes and inhibited the adipogenic program. This study clarified that adipogenesis was regulated by WGEF expression through DNA methylation change.
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Horii
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Morita
authors.forename: Mika
authors.initials: M
authors.lastname: Kimura
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
mesh_terms: D041721:3T3-L1 Cells / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C493893:WGEF protein, mouse; D054460:rho-Associated Kinases; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein