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Zhang X, Azhar G, Helms S, et al. Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts. Gene Regul Syst Bio. 2011;5:41-59doi: 10.4137/GRSB.S7457.
Zhang, X., Azhar, G., Helms, S., Burton, B., Huang, C., Zhong, Y., Gu, X., Fang, H., Tong, W., & Wei, J. Y. (2011). Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts. Gene regulation and systems biology, 541-59. https://doi.org/10.4137/GRSB.S7457
Zhang, Xiaomin, et al. "Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts." Gene regulation and systems biology vol. 5 (2011): 41-59. doi: https://doi.org/10.4137/GRSB.S7457
Zhang X, Azhar G, Helms S, Burton B, Huang C, Zhong Y, Gu X, Fang H, Tong W, Wei JY. Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts. Gene Regul Syst Bio. 2011;5:41-59. doi: 10.4137/GRSB.S7457. Epub 2011 Jul 12. PMID: 21792293; PMCID: PMC3140411.
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Gene Regul Syst Bio. 2011;5:41-59. doi: 10.4137/GRSB.S7457. Epub 2011 Jul 12.

Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.

Gene regulation and systems biology

Xiaomin Zhang, Gohar Azhar, Scott Helms, Brian Burton, Chris Huang, Ying Zhong, Xuesong Gu, Hong Fang, Weida Tong, Jeanne Y Wei

Affiliations

  1. Donald W. Reynolds Department of Geriatrics, The University of Arkansas for Medical Sciences and Geriatric Research, Education, and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.

PMID: 21792293 PMCID: PMC3140411 DOI: 10.4137/GRSB.S7457

Abstract

BACKGROUND: To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg).

METHODOLOGY: Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well.

CONCLUSION AND SIGNIFICANCE: SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart.

Keywords: SRF binding sites; SRF modulated genes; gene expression; mild-SRF over-expression; mouse heart; striated muscle

References

  1. Cell. 1994 Nov 4;79(3):427-36 - PubMed
  2. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):17970-5 - PubMed
  3. J Gerontol A Biol Sci Med Sci. 1998 Jan;53(1):B3-10 - PubMed
  4. Physiol Genomics. 2004 Sep 16;19(1):93-105 - PubMed
  5. Circ Res. 1998 Mar 23;82(5):566-75 - PubMed
  6. J Biol Chem. 2001 Oct 26;276(43):40033-40 - PubMed
  7. Cell. 1986 Aug 15;46(4):567-74 - PubMed
  8. Clin Biochem. 2009 Jun;42(9):819-22 - PubMed
  9. Mol Cell Biol. 1989 Feb;9(2):515-22 - PubMed
  10. Circulation. 2009 Oct 27;120(17):1695-703 - PubMed
  11. EMBO J. 2000 Nov 1;19(21):5835-44 - PubMed
  12. J Biol Chem. 1998 Apr 3;273(14):8398-406 - PubMed
  13. Neurobiol Aging. 2007 Dec;28(12):1795-809 - PubMed
  14. EMBO J. 2000 Sep 15;19(18):4955-66 - PubMed
  15. Prostaglandins Other Lipid Mediat. 2008 Mar;85(3-4):69-80 - PubMed
  16. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14988-93 - PubMed
  17. Nucleic Acids Res. 2007;35(14):4858-68 - PubMed
  18. Genomics. 1994 Nov 15;24(2):259-65 - PubMed
  19. Curr Opin Genet Dev. 1992 Apr;2(2):221-6 - PubMed
  20. Cell. 2001 Jun 29;105(7):851-62 - PubMed
  21. Development. 1989 May;106(1):67-78 - PubMed
  22. Clin Geriatr Med. 2000 Aug;16(3):419-44 - PubMed
  23. Clin Cancer Res. 2005 Aug 15;11(16):5730-9 - PubMed
  24. Nat Rev Genet. 2002 Feb;3(2):149-53 - PubMed
  25. BMC Bioinformatics. 2006 Sep 06;7 Suppl 2:S23 - PubMed
  26. Curr Cardiol Rep. 2008 Mar;10(2):142-8 - PubMed
  27. Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2480-97 - PubMed
  28. Mol Cell Biochem. 1998 Nov;188(1-2):49-56 - PubMed
  29. Nat Genet. 2000 May;25(1):25-9 - PubMed
  30. J Biol Chem. 2004 Feb 6;279(6):4782-93 - PubMed
  31. J Biol Chem. 2005 May 13;280(19):19115-26 - PubMed
  32. Kidney Int. 2005 Dec;68(6):2667-79 - PubMed
  33. J Mol Cell Cardiol. 2003 Jun;35(6):577-93 - PubMed
  34. N Engl J Med. 1992 Dec 10;327(24):1735-9 - PubMed
  35. Prog Lipid Res. 2006 May;45(3):237-49 - PubMed
  36. Annu Rev Biochem. 2000;69:343-72 - PubMed
  37. J Biol Chem. 2004 Dec 31;279(53):55626-32 - PubMed
  38. Neurosci Lett. 2008 Jul 4;439(1):100-5 - PubMed
  39. Exp Gerontol. 2006 Feb;41(2):189-204 - PubMed
  40. Hypertension. 2005 May;45(5):927-33 - PubMed
  41. Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):724-32 - PubMed
  42. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5184-8 - PubMed
  43. Am J Physiol Regul Integr Comp Physiol. 2003 Sep;285(3):R552-60 - PubMed
  44. Cell. 2003 Jan 10;112(1):113-22 - PubMed
  45. Exp Cell Res. 1996 Dec 15;229(2):432-7 - PubMed
  46. Biochem J. 2000 Feb 1;345 Pt 3:445-51 - PubMed
  47. J Neurochem. 1998 Oct;71(4):1643-50 - PubMed
  48. Am J Physiol Cell Physiol. 2007 Jan;292(1):C70-81 - PubMed
  49. J Clin Invest. 2008 Dec;118(12):3870-80 - PubMed
  50. Cardiovasc Res. 2005 Mar 1;65(4):793-802 - PubMed
  51. Cardiology. 1992;81(1):8-13 - PubMed
  52. Cardiovasc Res. 2000 Jan 14;45(2):279-93 - PubMed
  53. Heart Fail Rev. 2002 Apr;7(2):115-30 - PubMed
  54. EMBO J. 2004 Apr 21;23(8):1834-44 - PubMed
  55. BMC Proc. 2009 Dec 15;3 Suppl 7:S80 - PubMed
  56. Cold Spring Harb Symp Quant Biol. 2002;67:97-105 - PubMed
  57. J Cell Biochem. 2007 Jun 1;101(3):695-711 - PubMed
  58. J Biol Chem. 2007 Apr 27;282(17):12363-7 - PubMed
  59. FEBS Lett. 1995 Jun 5;366(1):53-6 - PubMed
  60. Cardiovasc Res. 2005 May 1;66(2):194-204 - PubMed
  61. Hum Mol Genet. 2004 Oct 1;13(19):2263-78 - PubMed
  62. Exp Neurol. 2003 Dec;184(2):697-704 - PubMed
  63. J Mol Cell Cardiol. 2006 Jan;40(1):56-63 - PubMed
  64. Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1581-9 - PubMed
  65. Am J Pathol. 2002 May;160(5):1831-7 - PubMed
  66. Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1782-92 - PubMed
  67. Nat Genet. 2006 Feb;38(2):228-33 - PubMed
  68. Circulation. 2009 Jul 28;120(4):318-25 - PubMed
  69. Biochem Biophys Res Commun. 2009 Aug 7;385(4):581-5 - PubMed
  70. Circ Res. 2007 Aug 3;101(3):313-21 - PubMed
  71. Gene. 2007 Oct 1;400(1-2):131-9 - PubMed
  72. Environ Health Perspect. 2003 Nov;111(15):1819-26 - PubMed
  73. Physiol Genomics. 2004 Feb 13;16(3):349-60 - PubMed
  74. Neurol Res. 2000 Jun;22(4):330-6 - PubMed
  75. Clin Chem. 2007 Feb;53(2):284-91 - PubMed
  76. Drugs Aging. 2001;18(4):263-76 - PubMed
  77. Lab Invest. 2003 May;83(5):743-57 - PubMed

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