title: Transcriptional regulation of mitochondrial glycerophosphate acyltransferase is mediated by distal promoter via ChREBP and SREBP-1.
abstract: We have recently identified two promoters, distal and proximal for rat mitochondrial glycerophosphate acyltransferase (mtGPAT). Here we are reporting further characterization of the promoters. Insulin and epidermal growth factor (EGF) stimulated while leptin and glucagon inhibited the luciferase activity of the distal promoter and the amounts of the distal transcript. Conversely, luciferase activity of the proximal promoter and proximal transcript remained unchanged due to these treatments. Only the distal promoter has binding sites for carbohydrate response element binding protein (ChREBP) and sterol regulatory element binding protein-1 (SREBP-1). Electromobility shift assays and chromatin immunoprecipitation assays demonstrated that ChREBP and SREBP-1 bind to the mtGPAT distal promoter. Insulin and EGF increased while glucagon and leptin decreased the binding of SREBP-1 and ChREBP to the distal promoter. Thus, the distal promoter is the regulatory promoter while the proximal promoter acts constitutively for rat mtGPAT gene under the influence of hormones and growth factor.
authors.affiliation: Department of Biological Sciences, St. John's University, Queens, NY 11439, USA.
authors.forename: Prajna
authors.initials: P
authors.lastname: Guha
authors.forename: Kawalpreet K
authors.initials: KK
authors.lastname: Aneja
authors.forename: Rasheda Y
authors.initials: RY
authors.lastname: Shilpi
authors.forename: Dipak
authors.initials: D
authors.lastname: Haldar
mesh_terms: D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D007328:Insulin; D020738:Leptin; C442825:Mlxipl protein, rat; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D004815:Epidermal Growth Factor; D005934:Glucagon; D008156:Luciferases; D005992:Glycerol-3-Phosphate O-Acyltransferase
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