May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
The number of AP–1– and NF–kB–DNA binding sites in gene promoters has a strong correlation with their extent of induction by HSV–1 following hyperthermic stress or immunosuppression
Author Affiliations & Notes
  • J.M. Hill
    Ophthalmology, LSU Eye Center, New Orleans, LA
  • H.W. Thompson
    Ophthalmology, LSU Eye Center, New Orleans, LA
  • W.J. Lukiw
    Ophthalmology, LSU Eye Center, New Orleans, LA
  • Footnotes
    Commercial Relationships  J.M. Hill, None; H.W. Thompson, None; W.J. Lukiw, None.
  • Footnotes
    Support  AG18031 (WJL), NEI06311 (JMH), EY02377 (LSU EYE CENTER CORE GRANT)
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2508. doi:
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      J.M. Hill, H.W. Thompson, W.J. Lukiw; The number of AP–1– and NF–kB–DNA binding sites in gene promoters has a strong correlation with their extent of induction by HSV–1 following hyperthermic stress or immunosuppression . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2508.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Using DNA arrays and gene profiling we recently reported that a specific set of genes in the trigeminal ganglion were rapidly reactivated by HSV–1 following short periods of heat stress or immunosuppression. These genes included those encoding heat shock proteins, DNA repair enzymes, several kinases, superoxide dismutase, peroxidase and cyclooxygenase–2. In an effort to further understand how these genes may be coordinately up–regulated, the DNA sequence of their immediate upstream promoters were analyzed for the type and number of DNA binding sites for transcription factor (TF) occupancy. Methods: BALB/c mice innoculated in the cornea with HSV–1 strain McKrae were used to examine the effects of hyperthermic stress and immunosuppression on gene expression pattens. Stress–mediated induction of HSV–1 and analysis of gene expression employed Nylon membrane–based DNA arrays (Atlas Clontech, Palo Alto, CA). From the accession numbers of up–regulated genes, mouse–specific promoter sequences were obtained using the Medline nucleotide search engine at www.ncbi.nih.nlm.gov. GenBank files containing immediate promoter DNA sequences were derived with nucleotide +1 representing the major start of transcription. TF searches were performed using DNASIS MAX Version 2.0 (MiraiBio, Hitachi Genetic Systems, Alameda, CA) or the BIOBASE TRANSFAC algorithms at www.biobase.de. Correlation between relative signal strength and TF occupancy of up–regulated promoters was determined using the Spearman Rank Order Correlation method. All statistical procedures were performed with the programs and procedures in the SAS language (Statistical Analysis System, SAS Institute, Cary, NC). Results: Of the TFs analyzed, the number of DNA binding sites for AP–1 and NF–kB in the promoters for all of the genes, plotted against the up–regulated gene expression signal, gave the most significant correlation (ρ=0.91). Other common TFs such as AP2 or SP1 showed no such correlation. These results suggest that the degree to which a gene is up–regulated after HSV–1 reactivation may be a function of how many [AP–1+NF–kB]–DNA binding sites are present in that gene's immediate promoter. Conclusions: Specific families of TFs, in combination with defined chromatin structures within gene regulatory regions, can recruit specific gene families during coordinated gene expression. These observations provide a rational basis for understanding what families of genes are induced during complex genetic responses to physiological, viral, pharmacological and environmental stress.

Keywords: gene/expression • gene modifiers • herpes simplex virus 
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