title: CCAAT/enhancer-binding protein α is a crucial regulator of human fat mass and obesity associated gene transcription and expression.
abstract: Several susceptibility loci have been reported associated with obesity and T2DM in GWAS. Fat mass and obesity associated gene (FTO) is the first gene associated with body mass index (BMI) and risk for diabetes in diverse patient populations. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. While much is known about the epigenetic mutations contributing to obesity and T2DM, less is certain with the expression regulation of FTO gene. In this study, a highly conserved canonical C/EBP α binding site was located around position -45~-54 bp relative to the human FTO gene transcriptional start site. Site-directed mutagenesis of the putative C/EBP α binding sites decreased FTO promoter activity. Overexpression and RNAi studies also indicated that C/EBP α was required for the expression of FTO. Chromatin immunoprecipitation (ChIP) experiment was carried out and the result shows direct binding of C/EBP α to the putative binding regions in the FTO promoter. Collectively, our data suggest that C/EBP α may act as a positive regulator binding to FTO promoter and consequently, activates the gene transcription.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai 200233, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
authors.forename: Jianjin
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai 200233, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai 200233, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Li
authors.affiliation: The Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xiubin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai 200233, China.
authors.forename: Weiping
authors.identifier: 0000-0002-6244-2168
authors.initials: W
authors.lastname: Jia
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human