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Regulation of phosphoenolpyruvate carboxykinase gene transcription by thyroid hormone involves two distinct binding sites in the promoter. 1995

E A Park, and D C Jerden, and S W Bahouth
Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis 38163, USA.

Transcription of the gene for phosphoenolpyruvate carboxy-kinase (PEPCK) is stimulated by thyroid hormone (T3), glucagon (via cyclic AMP) and glucocorticoids. A region of the PEPCK promoter between -332 and -308 mediates the induction of transcription by T3. To characterize this region further, mutations were introduced into this region of the PEPCK promoter and the modified promoters ligated to the chloramphenicol acetyltransferase (CAT) reporter gene. Using these PEPCK-CAT vectors in transient transfections in HepG2 cells, it was found that T3 stimulates PEPCK transcription through two direct repeats of the AGGTCA motif located between nucleotides -330 and -319 [PEPCK-thyroid-hormone-responsive element (TRE)]. The beta form of the T3 receptor (TR beta) bound PEPCK-TRE as a homodimer but bound far more efficiently as a heterodimeric complex with the retinoid X receptor (RXR). An additional region called P3(I) (-250 to -234) is required for T3 responsiveness and binds members of the CCAAT-enhancer-binding protein (C/EBP) family. P3(I) contains an AGGTCA-like motif that can bind the TR beta-RXR heterodimer. Mutagenesis of this motif abolished TR beta-RXR binding without reducing T3 induction. Mutation of the C/EBP-binding site or insertion of a cyclic AMP-responsive-binding-protein site at P3(I) eliminated the T3 response. Our results indicate that T3 stimulation of PEPCK transcription is mediated by TR beta bound to PEPCK-TRE and requires C/EBP to be bound at the P3(I) site.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010729 Phosphoenolpyruvate Carboxykinase (GTP) An enzyme of the lyase class that catalyzes the conversion of GTP and oxaloacetate to GDP, phosphoenolpyruvate, and carbon dioxide. This reaction is part of gluconeogenesis in the liver. The enzyme occurs in both the mitochondria and cytosol of mammalian liver. (From Dorland, 27th ed) EC 4.1.1.32. GTP-Dependent Phosphoenolpyruvate Carboxykinase,Carboxykinase, GTP-Dependent Phosphoenolpyruvate,GTP Dependent Phosphoenolpyruvate Carboxykinase,Phosphoenolpyruvate Carboxykinase, GTP-Dependent
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D011988 Receptors, Thyroid Hormone Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively. Diiodotyrosine Receptors,Receptors, Diiodotyrosine,Receptors, Thyroxine,Receptors, Triiodothyronine,T3 Receptors,T4 Receptors,Thyroid Hormone Receptors,Thyroxine Receptors,Triiodothyronine Receptors,DIT Receptors,Diiodotyrosine Receptor,MIT Receptors,Monoiodotyrosine Receptors,Receptors, DIT,Receptors, MIT,Receptors, Monoiodotyrosine,Receptors, T3,Receptors, T4,T3 Receptor,T4 Receptor,Thyroid Hormone Receptor,Thyroxine Receptor
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining

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