Glucose regulation of mouse S(14) gene expression in hepatocytes. Involvement of a novel transcription factor complex.

Transcription of genes encoding enzymes required for lipogenesis is induced in hepatocytes in response to elevated glucose metabolism. We have previously mapped the carbohydrate-response elements (ChoREs) of the rat liver-type pyruvate kinase (L-PK) and S(14) genes and found them to share significant sequence similarity. However, progress in unraveling this signaling pathway has been hampered due to the difficulty in identifying the key factor(s) that bind to these ChoREs. To gain further insight into the nature of the carbohydrate-responsive transcription factor, the glucose regulatory sequences from the mouse S(14) gene were examined in primary hepatocytes. Three elements were found to be essential for supporting the glucose response: a thyroid hormone-response element between -1522 and -1494, an accessory factor site between -1421 and -1392, and the ChoRE between -1450 and -1425. Of these, only the accessory factor site was conserved between the rat and mouse S(14) genes. Investigation of the ChoRE sequence indicated that two half E box motifs are critical for the response to glucose. Electrophoretic mobility shift assays revealed a complex formed between the mouse S(14) ChoRE and liver nuclear proteins. This complex was also formed by ChoREs from the rat S(14) and L-PK genes but not by mutants of these sites that are inactive in supporting the glucose response. These results suggest the presence of a novel transcription factor complex that mediates the glucose-regulated transcription of S(14) and L-PK genes.

[1]  B. Spiegelman,et al.  ADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose , 1999, Molecular and Cellular Biology.

[2]  T. Tanaka,et al.  Characterization and purification of carbohydrate response element-binding protein of the rat L-type pyruvate kinase gene promoter. , 1999, Biochemical and biophysical research communications.

[3]  J. Hasegawa,et al.  A Novel Factor Binding to the Glucose Response Elements of Liver Pyruvate Kinase and Fatty Acid Synthase Genes* , 1999, The Journal of Biological Chemistry.

[4]  T. Osborne,et al.  Molecular aspects in feedback regulation of gene expression by cholesterol in mammalian cells. , 1998, Methods.

[5]  S. Vaulont,et al.  Differential Roles of Upstream Stimulatory Factors 1 and 2 in the Transcriptional Response of Liver Genes to Glucose* , 1998, The Journal of Biological Chemistry.

[6]  I. Shimomura,et al.  Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Dooley,et al.  Sterol Regulation of 3-Hydroxy-3-Methylglutaryl-coenzyme A Synthase Gene through a Direct Interaction Between Sterol Regulatory Element Binding Protein and the Trimeric CCAAT-binding Factor/Nuclear Factor Y* , 1998, The Journal of Biological Chemistry.

[8]  S. Vaulont,et al.  Glucose-dependent Liver Gene Expression in Upstream Stimulatory Factor 2 −/− Mice* , 1997, The Journal of Biological Chemistry.

[9]  J. Goldstein,et al.  The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor , 1997, Cell.

[10]  H. Shih,et al.  Carbohydrate Regulation of Hepatic Gene Expression , 1997, The Journal of Biological Chemistry.

[11]  R. Hammer,et al.  Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. , 1997, The Journal of clinical investigation.

[12]  I. Shimomura,et al.  Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. , 1997, The Journal of clinical investigation.

[13]  Marybeth I. Maloney,et al.  “Spot 14” Protein Functions at the Pretranslational Level in the Regulation of Hepatic Metabolism by Thyroid Hormone and Glucose* , 1997, The Journal of Biological Chemistry.

[14]  P. Reynier,et al.  Cloning and initial characterization of human and mouse Spot 14 genes 1 , 1997, FEBS letters.

[15]  P. Edwards,et al.  Synergistic Binding of Sterol Regulatory Element-binding Protein and NF-Y to the Farnesyl Diphosphate Synthase Promoter Is Critical for Sterol-regulated Expression of the Gene* , 1996, The Journal of Biological Chemistry.

[16]  R. Hammer,et al.  Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. , 1996, The Journal of clinical investigation.

[17]  J. Girard,et al.  Regulation of lipogenic enzyme expression by glucose in liver and adipose tissue: is glucose 6-phosphate the signalling metabolite? , 1996, Biochemical Society transactions.

[18]  S. Clarke,et al.  Polyunsaturated fatty acid regulation of hepatic gene transcription. , 1996, The Journal of nutrition.

[19]  Ruihuan Chen,et al.  Transcriptional Glucose Signaling through The Glucose Response Element Is Mediated by the Pentose Phosphate Pathway (*) , 1996, The Journal of Biological Chemistry.

[20]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[21]  H. Shih,et al.  Two CACGTG Motifs with Proper Spacing Dictate the Carbohydrate Regulation of Hepatic Gene Transcription (*) , 1995, The Journal of Biological Chemistry.

[22]  C. Mariash,et al.  Direct Evidence for a Role of the "Spot 14" Protein in the Regulation of Lipid Synthesis (*) , 1995, The Journal of Biological Chemistry.

[23]  H. Towle,et al.  Functional synergism in the carbohydrate-induced activation of liver-type pyruvate kinase gene expression. , 1995, The Biochemical journal.

[24]  B. Spiegelman,et al.  Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain , 1995, Molecular and cellular biology.

[25]  H. Shih,et al.  Matrigel treatment of primary hepatocytes following DNA transfection enhances responsiveness to extracellular stimuli. , 1995, BioTechniques.

[26]  A. Kahn,et al.  Upstream Stimulatory Factor Proteins Are Major Components of the Glucose Response Complex of the L-type Pyruvate Kinase Gene Promoter (*) , 1995, The Journal of Biological Chemistry.

[27]  T. Osborne,et al.  Cooperation by Sterol Regulatory Element-binding Protein and Sp1 in Sterol Regulation of Low Density Lipoprotein Receptor Gene (*) , 1995, The Journal of Biological Chemistry.

[28]  A. Kahn,et al.  Respective roles of glucose, fructose, and insulin in the regulation of the liver-specific pyruvate kinase gene promoter. , 1994, The Journal of biological chemistry.

[29]  H. Shih,et al.  Definition of the carbohydrate response element of the rat S14 gene. Context of the CACGTG motif determines the specificity of carbohydrate regulation. , 1994, The Journal of biological chemistry.

[30]  M. Díaz-Guerra,et al.  Glucose‐dependent regulation of the l‐pyruvate kinase gene in a hepatoma cell line is independent of insulin and cyclic AMP , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  S. Vaulont,et al.  Transcriptional control of metabolic regulation genes by carbohydrates , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  A. Kahn,et al.  Functional characterization of the L-type pyruvate kinase gene glucose response complex , 1993, Molecular and cellular biology.

[33]  H. Towle,et al.  Carbohydrate regulation of the rat L-type pyruvate kinase gene requires two nuclear factors: LF-A1 and a member of the c-myc family. , 1993, The Journal of biological chemistry.

[34]  H. Shih,et al.  Definition of the carbohydrate response element of the rat S14 gene. Evidence for a common factor required for carbohydrate regulation of hepatic genes. , 1992, The Journal of biological chemistry.

[35]  M. Díaz-Guerra,et al.  Cis-regulation of the L-type pyruvate kinase gene promoter by glucose, insulin and cyclic AMP. , 1992, Nucleic acids research.

[36]  H. Towle,et al.  Localization of the carbohydrate response element of the rat L-type pyruvate kinase gene. , 1991, The Journal of biological chemistry.

[37]  D. Jump,et al.  Thyroid hormone and dietary carbohydrate interact to regulate rat liver S14 gene transcription and chromatin structure. , 1990, The Journal of biological chemistry.

[38]  H. Towle,et al.  Sequences within the 5'-flanking region of the S14 gene confer responsiveness to glucose in primary hepatocytes. , 1989, The Journal of biological chemistry.

[39]  S. Vaulont,et al.  Proteins binding to the liver-specific pyruvate kinase gene promoter. A unique combination of known factors. , 1989, Journal of molecular biology.

[40]  C. Mariash,et al.  Rapid synergistic interaction between thyroid hormone and carbohydrate on mRNAS14 induction. , 1986, The Journal of biological chemistry.

[41]  D. Jump,et al.  High basal expression and 3,5,3'-triiodothyronine regulation of messenger ribonucleic acid S14 in lipogenic tissues. , 1985, Endocrinology.

[42]  C. Mariash,et al.  T3 stimulates the synthesis of a specific mRNA in primary hepatocyte culture. , 1984, Biochemical and biophysical research communications.

[43]  P. Narayan,et al.  Rapid induction of a specific nuclear mRNA precursor by thyroid hormone. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[44]  H. Towle,et al.  Interactions of thyroid hormone, growth hormone, and high carbohydrate, fat-free diet in regulating several rat liver messenger ribonucleic acid species. , 1983, Biochemistry.

[45]  H. Towle,et al.  Thyroid hormone attenuates and augments hepatic gene expression at a pretranslational level. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[46]  H. Towle,et al.  Synergism of thyroid hormone and high carbohydrate diet in the induction of lipogenic enzymes in the rat. Mechanisms and implications. , 1980, The Journal of clinical investigation.

[47]  L. Gourdon,et al.  Effect of different basic helix-loop-helix leucine zipper factors on the glucose response unit of the L-type pyruvate kinase gene. , 1998, Gene expression.

[48]  B. Spiegelman,et al.  Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. , 1998, The Journal of clinical investigation.

[49]  J. Girard,et al.  Mechanisms by which carbohydrates regulate expression of genes for glycolytic and lipogenic enzymes. , 1997, Annual review of nutrition.

[50]  H. Shih,et al.  Regulation of the expression of lipogenic enzyme genes by carbohydrate. , 1997, Annual review of nutrition.

[51]  A. Goodridge,et al.  Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis. , 1995, Physiological reviews.