title: Srebf1a is a key regulator of transcriptional control for adipogenesis.
abstract: Adipogenesis is regulated by a complex cascade of transcriptional factors, but little is known about the early events that regulate the adipogenic program. Here, we report the role of the srebf1a gene in the differentiation of fibroblastic 3T3-F442A cells. We found that expression of srebf1a depended on GSK3β activity and that GSK3β activity was necessary for C/EBPβ phosphorylation at Thr188. Knockdown of srebf1a inhibited the adipogenic program because it blocked the expression of genes encoding PPARγ2, C/EBPα, SREBP1c and even FABP4, demonstrating that SREBP1a activation is upstream of these three essential adipogenic transcription factors. Kinetic analysis during differentiation illustrated that the order of expression of adipogenic genes was the following: cebpb, srebf1a, pparg2, cebpa, srebp1c and fabp4. Our data suggest that srebf1a acts as an essential link between the GSK3β-C/EBPβ signaling axis and the beginning of the adipogenic transcriptional cascade.
authors.affiliation: Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del Instituto Politcénico Nacional, Mexico City, Federal District, 07360, Mexico.
authors.forename: Jorge-Tonatiuh
authors.initials: JT
authors.lastname: Ayala-Sumuano
authors.forename: Cristina
authors.initials: C
authors.lastname: Velez-Delvalle
authors.forename: Alicia
authors.initials: A
authors.lastname: Beltrán-Langarica
authors.forename: Meytha
authors.initials: M
authors.lastname: Marsch-Moreno
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerbón-Solorzano
authors.forename: Walid
authors.initials: W
authors.lastname: Kuri-Harcuch
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D047495:PPAR gamma; D020033:Protein Isoforms; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3