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cAMP increases the expression of human angiotensinogen gene through a combination of cyclic AMP responsive element binding protein and a liver specific transcription factor

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Abstract

Angiotensinogen is the glycoprotein precursor of one of the most potent vasoactive hormones angiotensin-II which plays an important role in the regulation of blood pressure. We show here that the promoter activity of reporter constructs containing human angiotensinogen promoter is increased by cAMP treatment on transient transfection in HepG2 cells. We have identified a composite cAMP responsive element, located around 840 bases upstream from the transcriptional initiation site, in the promoter of human angiotensinogen gene. This element is recognized by members of CREB/ATF as well as C/EBP family of transcription factors. Another C/EBP binding site that is not recognized by CREB is located 10 bases upstream from this site. We show that co-transfection of CREB increases the promoter activity of reporter constructs containing human angiotensinogen gene promoter attached to the CAT gene. We also show that co-transfection of DBP (which is a member of C/EBP family of transcription factors) increases promoter activity of these reporter constructs.

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References

  1. Corvol P, Jeunemaitre X, Charru A, Kotelevtsev Y, Soubrier F: Role of the renin-angiotensin system in blood pressure regulation and in human hypertension: new insights from molecular genetics. Rec Prog Horm Res 50: 287–308, 1995

    Google Scholar 

  2. Brasier AR, Li J: Mechanisms for inducible control of angiotensinogen gene transcription. Hypertension 27: 465–475, 1996

    Google Scholar 

  3. Mancia G, Grassi G, Giannattasio C, Seravalle G: Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 34: 724–728, 1999

    Google Scholar 

  4. Mancia G: Bjorn Folkow Award Lecture. The sympathetic nervous system in hypertension. J Hypertens 15: 1553–1565, 1997

    Google Scholar 

  5. Ying L, Morris BJ, Sigmund CD: Transactivation of the human renin promoter by the cyclic AMP/protein kinase A pathway is mediated by both cAMP-responsive element binding protein-1 (CREB)-dependent and CREB-independent mechanisms in Calu-6 cells. J Biol Chem 272: 2412–2420, 1997

    Google Scholar 

  6. Germain S, Konoshita T, Philippe J, Corvol P, Pinet F: Transcriptional induction of the human renin gene by cyclic AMP requires cyclic AMP response element-binding protein (CREB) and a factor binding a pituitary-specific trans-acting factor (Pit-1) motif. Biochem J 316 (Part 1): 107–113, 1996

    Google Scholar 

  7. Tamura K, Umemura S, Yamaguchi S, Iwamoto T, Kobayashi S, Fukamizu A, Murakami K, Ishii M: Mechanism of cAMP regulation of renin gene transcription by proximal promoter. J Clin Invest 94: 1959–1967, 1994

    Google Scholar 

  8. Ohtani R, Yayama K, Takano M, Itoh N, Okamoto H: Stimulation of angiotensinogen production in primary cultures of rat hepatocytes by glucocorticoid, cyclic adenosine 3′,5′-monophosphate, and interleukin-6. Endocrinology 130: 1331–1338, 1992

    Google Scholar 

  9. Ming M, Wu J, Lachance S, Delalandre A, Carriere S, Chan JS: Betaadrenergic receptors and angiotensinogen gene expression in mouse hepatoma cells in vitro. Hypertension 25: 105–109, 1995

    Google Scholar 

  10. Montminy M: Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66: 807–822, 1997

    Google Scholar 

  11. Meyer TE, Habener JF: Cyclic adenosine 3′,5′-monophosphate response element binding protein (CREB) and related transcription-activating deoxyribonucleic acid-binding proteins. Endocr Rev 14: 269–290, 1993

    Google Scholar 

  12. Hoeffler JP, Meyer TE, Yun Y, Jameson JL, Habener JF: Cyclic AMPresponsive DNA-binding protein: Structure based on a cloned placental cDNA. Science 242: 1430–1433, 1988

    Google Scholar 

  13. Gonzalez GA, Yamamoto KK, Fischer WH, Karr D, Menzel P, Biggs W3, Vale WW, Montminy MR: A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence. Nature 337: 749–752, 1989

    Google Scholar 

  14. Gonzalez GA, Montminy MR: Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59: 675–680, 1989

    Google Scholar 

  15. Lamph WW, Dwarki VJ, Ofir R, Montminy M, Verma IM: Negative and positive regulation by transcription factor cAMP response elementbinding protein is modulated by phosphorylation. Proc Natl Acad Sci USA 87: 4320–4324, 1990

    Google Scholar 

  16. Yamamoto KK, Gonzalez GA, Menzel P, Rivier J, Montminy MR: Characterization of a bipartite activator domain in transcription factor CREB. Cell 60: 611–617, 1990

    Google Scholar 

  17. Dwarki VJ, Montminy M, Verma IM: Both the basic region and the ‘leucine zipper’ domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation. EMBO J 9: 225–232, 1990

    Google Scholar 

  18. Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH: Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365: 855–859, 1993

    Google Scholar 

  19. Parker D, Ferreri K, Nakajima T, LaMorte VJ, Evans R, Koerber SC, Hoeger C, Montminy MR: Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol Cell Biol 16: 694–703, 1996

    Google Scholar 

  20. Goldman PS, Tran VK, Goodman RH: The multifunctional role of the co-activator CBP in transcriptional regulation. Rec Prog Horm Res 52: 103–119, 1997

    Google Scholar 

  21. Hai TW, Liu F, Coukos WJ, Green MR: Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers (published erratum appears in Genes Dev 4: 682, 1990). Genes Dev 3: 2083–2090, 1989

    Google Scholar 

  22. Foulkes NS, Borrelli E, Sassone Corsi P: CREM gene: Use of alternative DNA-binding domains generates multiple antagonists of cAMPinduced transcription. Cell 64: 739–749, 1991

    Google Scholar 

  23. Fimia GM, De Cesare D, Sassone-Corsi P: CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature 398: 165–169, 1999

    Google Scholar 

  24. Campbell DJ, Habener JF: Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest 78: 31–39, 1986

    Google Scholar 

  25. Narayanan CS, Cui Y, Kumar A: DBP binds to the proximal promoter and regulates liver-specific expression of the human angiotensinogen gene. Biochem Biophys Res Commun 251: 388–393, 1998

    Google Scholar 

  26. Cui Y, Narayanan CS, Zhou J, Kumar A: Exon-I is involved in positive as well as negative regulation of human angiotensinogen gene expression. Gene 224: 97–107, 1998

    Google Scholar 

  27. Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K: Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem 265: 7576–7582, 1990

    Google Scholar 

  28. Zhao YY, Zhou J, Kumar A. Molecular mechanism of human essential hypertension: A mutation in the proximal promoter of the angiotensinogen gene from hypertensive patients increases its transcription in human hepatoma cells. Circulation 94(suppl 1): (abstr) I–693, 1996

    Google Scholar 

  29. Zhao YY, Zhou J, Narayanan CS, Cui Y, Kumar A: Role of C/A polymorphism at-20 on the expression of human angiotensinogen gene. Hypertension 33: 108–115, 1999

    Google Scholar 

  30. Yanai K, Nibu Y, Murakami K, Fukamizu A: A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene. J Biol Chem 271: 15981–15986, 1996

    Google Scholar 

  31. Narayanan CS, Cui Y, Zhao YY, Zhou J, Kumar A: Orphan receptor Arp-1 binds to the nucleotide sequence located between TATA box and transcriptional initiation site of the human angiotensinogen gene and reduces estrogen induced promoter activity. Mol Cell Endocrinol 148: 79–86, 1999

    Google Scholar 

  32. Dignam JD, Lebovitz RM, Roeder RG: Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucl Acids Res 11: 1475–1489, 1983

    Google Scholar 

  33. Friedman AD, Landschulz WH, McKnight SL: CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. Genes Dev 3: 1314–1322, 1989

    Google Scholar 

  34. Friedman AD, McKnight SL: Identification of two polypeptide segments of CCAAT/enhancer-binding protein required for transcriptional activation of the serum albumin gene. Genes Dev 4: 1416–1426, 1990

    Google Scholar 

  35. Vinson CR, Sigler PB, McKnight SL: Scissors-grip model for DNA recognition by a family of leucine zipper proteins. Science 246: 911–916, 1989

    Google Scholar 

  36. Vallejo M, Ron D, Miller CP, Habener JF: C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to cAMP response elements. Proc Natl Acad Sci USA 90: 4679–4683, 1993

    Google Scholar 

  37. Hai T, Curran T: Cross-family dimerization of transcription factors Fos/ Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci USA 88: 3720–3724, 1991

    Google Scholar 

  38. Hanson RW, Reshef L: Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Annu Rev Biochem 66: 581–611, 1997

    Google Scholar 

  39. Weih F, Stewart AF, Boshart M, Nitsch D, Schutz G: In vivo monitoring of a cAMP-stimulated DNA-binding activity. Genes Dev 4: 1437–1449, 1990

    Google Scholar 

  40. Nitsch D, Boshart M, Schutz G: Activation of the tyrosine aminotransferase gene is dependent on synergy between liver-specific and hormone-responsive elements. Proc Natl Acad Sci USA 90: 5479–5483, 1993

    Google Scholar 

  41. Chu HM, Tan Y, Kobierski LA, Balsam LB, Comb MJ: Activating transcription factor-3 stimulates 3′,5′-cyclic adenosine monophosphatedependent gene expression. Mol Endocrinol 8: 59–68, 1994

    Google Scholar 

  42. Tsukada J, Saito K, Waterman WR, Webb AC, Auron PE: Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 beta gene. Mol Cell Biol 14: 7285–7297, 1994

    Google Scholar 

  43. Nichols M, Weih F, Schmid W, DeVack C, Kowenz-Leutz E, Luckow B, Boshart M, Schutz G: Phosphorylation of CREB affects its binding to high and low affinity sites: Implications for cAMP induced gene transcription. EMBO J 11: 3337–3346, 1992

    Google Scholar 

  44. Chan JS, Chan AH, Jiang Q, Nie ZR, Lachance S, Carriere S: Molecular cloning and expression of the rat angiotensinogen gene. Pediatr Nephrol 4: 429–435, 1990

    Google Scholar 

  45. Qian JF, Wang TT, Wu XH, Wu J, Ge C, Lachance S, Carriere S, Chan JS: Angiotensinogen gene expression is stimulated by the cAMP-responsive element binding protein in opossum kidney cells. J Am Soc Nephrol 8: 1072–1079, 1997

    Google Scholar 

  46. Leahy P, Crawford DR, Grossman G, Gronostajski RM, Hanson RW: CREB binding protein coordinates the function of multiple transcription factors including nuclear factor I to regulate phosphoenolpyruvate carboxykinase (GTP) gene transcription. J Biol Chem 274: 8813–8822, 1999

    Google Scholar 

  47. Roesler WJ, Graham JG, Kolen R, Klemm DJ, McFie PJ: The cAMP response element binding protein synergizes with other transcription factors to mediate cAMP responsiveness. J Biol Chem 270: 8225–8232, 1995

    Google Scholar 

  48. Niehof M, Manns MP, Trautwein C: CREB controls LAP/C/EBP beta transcription. Mol Cell Biol 17: 3600–3613, 1997

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, New York Medical College, Valhalla, NY, 10530, USA

    Chittampalli S. Narayanan, Yanning Cui, Shubhra Kumar & Ashok Kumar

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  1. Chittampalli S. Narayanan
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  3. Shubhra Kumar
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Narayanan, C.S., Cui, Y., Kumar, S. et al. cAMP increases the expression of human angiotensinogen gene through a combination of cyclic AMP responsive element binding protein and a liver specific transcription factor. Mol Cell Biochem 212, 81–90 (2000). https://doi.org/10.1023/A:1007180322263

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