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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-6-11
pubmed:abstractText
Refeeding carbohydrate to fasted rats induces the transcription of genes encoding enzymes of fatty acid biosynthesis, e.g. fatty-acid synthase (FAS). Part of this transcriptional induction is mediated by insulin. An insulin response element has been described for the fatty-acid synthase gene region of -600 to +65, but the 2-3-fold increase in fatty-acid synthase promoter activity attributable to this region is small compared with the 20-30-fold induction in fatty-acid synthase gene transcription observed in fasted rats refed carbohydrate. We have previously reported that the fatty-acid synthase gene region between -7382 and -6970 was essential for achieving high in vivo rates of gene transcription. The studies of the current report demonstrate that the region of -7382 to -6970 of the fatty-acid synthase gene contains a carbohydrate response element (CHO-RE(FAS)) with a palindrome sequence (CATGTGn(5)GGCGTG) that is nearly identical to the CHO-RE of the l-type pyruvate kinase and S(14) genes. The glucose responsiveness imparted by CHO-RE(FAS) was independent of insulin. Moreover, CHO-RE(FAS) conferred glucose responsiveness to a heterologous promoter (i.e. l-type pyruvate kinase). Electrophoretic mobility shift assays demonstrated that CHO-RE(FAS) readily bound a unique hepatic ChoRF and that CHO-RE(FAS) competed with the CHO-RE of the l-type pyruvate kinase and S(14) genes for ChoRF binding. In vivo footprinting revealed that fasting reduced and refeeding increased ChoRF binding to CHO-RE(FAS). Thus, carbohydrate responsiveness of rat liver fatty-acid synthase appears to require both insulin and glucose signaling pathways. More importantly, a unique hepatic ChoRF has now been shown to recognize glucose responsive sequences that are common to three different genes: fatty-acid synthase, l-type pyruvate kinase, and S(14).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21969-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11279238-Animals, pubmed-meshheading:11279238-Base Sequence, pubmed-meshheading:11279238-Binding Sites, pubmed-meshheading:11279238-Cells, Cultured, pubmed-meshheading:11279238-DNA Footprinting, pubmed-meshheading:11279238-Fatty Acid Synthetase Complex, pubmed-meshheading:11279238-Gene Expression Regulation, Enzymologic, pubmed-meshheading:11279238-Glucose, pubmed-meshheading:11279238-Hepatocytes, pubmed-meshheading:11279238-Liver, pubmed-meshheading:11279238-Luciferases, pubmed-meshheading:11279238-Mice, pubmed-meshheading:11279238-Nuclear Proteins, pubmed-meshheading:11279238-Pyruvate Kinase, pubmed-meshheading:11279238-Rats, pubmed-meshheading:11279238-Rats, Sprague-Dawley, pubmed-meshheading:11279238-Sequence Alignment, pubmed-meshheading:11279238-Sequence Homology, Nucleic Acid, pubmed-meshheading:11279238-Transcription, Genetic, pubmed-meshheading:11279238-Transfection
pubmed:year
2001
pubmed:articleTitle
Involvement of a unique carbohydrate-responsive factor in the glucose regulation of rat liver fatty-acid synthase gene transcription.
pubmed:affiliation
Division of Nutritional Sciences and the Institute for Cellular and Molecular Biology, The University of Texas, Austin, Texas, 78712, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't