Enhanced links by

 

Herpes simplex (HSV-1) interacts with a number of host transcription factors, certain of which are depicted in this table.  When binding to the virus, their interaction with human genes is obviously impaired. These transcription factors control the expressionof many of the genes implicated in Alzheimer’s disease, as shown.  Genes reportedly associated with Alzheimer’s disease are in bold type.

This supplementary table relates to the publication:- "Interactions between the products of the Herpes simplex genome and Alzheimer's disease susceptibility genes: Relevance to pathological signalling cascades" Neurochem.Int 52, 920-934, 2008

Host Transcription Factor

Viral interactions

Alzheimer’s disease susceptibility candidates controlled by transcription factor

GABPA

GABPB2

GABPA (one of several genes known as nuclear respiratory factor 2) and GABPB2 control the expression of Herpes viral intermediate genes via an interaction with the viral ICP4 promoter 25.

PSEN193 and mitochondrial respiratory genes via the control of the mitochondrial transcription factor TFAM 120.

MEF2A

The ICP0 protein of HSV1 interacts with certain histone deacetylases (HDAC4, 5 and 9) via an amino terminal domain responsible for suppressing the activity of myocyte enhance factor MEF2A by nuclear sequestration.  ICP0 overcomes the HDAC mediated suppression of MEF2A 76

BACE1 69.

POU2F1

VP16 associates with host cell factor-1 (HCF1) and the transcription factor oct-1 (POU2F1) forming a complex responsible for the transcription of viral immediate early genes 77,125.

BACE2 79, BCHE 53, CCR2 126, (CRP) 121, LPL 97OLR1 9, TNF 47.

NFKB1

HSV-1 infection results in an early activation of the transcription factor nuclear factor kappa beta (NFKB1) an effect mediated via the viral proteins ICP4 and ICP2743. 

A2M2, ABCA1 11,APOE 26, APP 37, AR 108, BACE1100, CCL2 116,CRP 121,133, CYP19AS1 28, FAS 5, GSK3B 22, ICAM1 8, IL1B 46, IL1RN 33. IL6 80, MMP1, MMP3 3NOS3 18, OLR110, PLAU 42, PTGS2 105, TGFB1 73, TNF 56.  NFKB also downregulates the transcriptional activity of the AICD/APBB1 activator.  AICD is a gamma-secretase cleaved product of APP133.

SP1

Herpes simplex infection increases SP1 phosphorylation, an effect involving ICP4 and ICP27SP1 phosphorylation reduces its transcriptional efficacy63.

ABCA1 106, ABCA2 19, ACE 27, ADRB1 89, ALDH2 110, APOA141, APOC3 61, APOE 6, APP 95, APBB1 49, AR 112, ARSA 65, BACE1 15, BACE2 79, C4A 118, CCL2 67,CDC2 115, CETP 111CHAT 52,CHRNA3 31, COL11A1 131, CYP19A1 134, CST3 86, CTSD 98, DLD 29, DLST 85,ESR1 20, FGF194, HFE 83, HSPG2 16, ICAM1 130, IL1A 81, IL1B 50, IL6 102,LDLR1, LPL 128, MAOA 90, MAPT 44, MME 107, MPO 59, MTHFR 48,MTRR 72,NOS1 104, NOS3 60, OPRS1 96, TF 74, PARP1 132, PLAT 32, PLAU 51, PON1 4, POU2F1 39, PNMT 109, PPARA 13, PRNP 78, PSEN1 92PSEN2 99, PTGS2 117, RUNX1 36, SERPINE1 12, SLC6A4 45, SOAT1 127, TFAM 114,TGFB1 64, TNF 103, TP73 24, VEGFA 113

STAT1

Binds to the LAT promoter 66

APOE 68, BACE1 14, CCL2 119, FAS 57,  FCERG1 30,  ICAM1 7, SOAT1 127.

TFCP2

The herpes simplex genome contains three origins of replication sites, one of which contains concensus binding sites for the transcription factors NF-1 and CP2 (TFCP2)17

ESR1 70GSK3B 71.

USF1

USF2

The LAT promoter binds to the host USF transcription factor family 62

ABCA1129, APOC3 91APOE 101APP 122, CDC2 87CTSD  123, CYP19A1 54, ESR1 21, PAI1 23 and TGFB1 124.

YY1

A number of viral genes (ICP0, US5, UL19, UL27, UL37, UL48) bind to the host transcription factor yin-yang-1 (YY1) which controls their expression 38,75,82

BACE169, FAS34,  IL440, NOS3 60PARP1 88,  PTGS2 55 SREBF1 1,84 and TFCP258. YY1 also controls the expression of many cholesterol and lipoprotein-related genes via an interaction with sterol regulatory binding protein sites (SREBF1).  YY1 binds to Srebp1a and disrupts its binding to the sterol-response element.  Via this interaction it represses the SRE-mediated expression of the lipoprotein receptor LDLR as well as that of the steroidogenic acute regulatory protein (StAR) 1,84.  Conversely YY1 positively controls the expression of the cholesteryl ester transfer protein (CETP) 35.

REST A Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE) is located between HSV-1 genes ICP22 and ICP4.Pinnoji et al, 2007 In progress

 

 

 

 

Reference List

     1.    Bennett, M. K., T. T. Ngo, J. N. Athanikar, J. M. Rosenfeld, and T. F. Osborne. 1999. Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein. J Biol. Chem. 274:13025-13032.

     2.    Bode, J. G., R. Fischer, D. Haussinger, L. Graeve, P. C. Heinrich, and F. Schaper. 2001. The inhibitory effect of IL-1 beta on IL-6-induced alpha 2-macroglobulin expression is due to activation of NF-kappa B. J Immunol. 167:1469-1481.

     3.    Bond, M., A. J. Chase, A. H. Baker, and A. C. Newby. 2001. Inhibition of transcription factor NF-kappaB reduces matrix metalloproteinase-1, -3 and -9 production by vascular smooth muscle cells. Cardiovasc. Res. 50:556-565.

     4.    Brophy, V. H., M. D. Hastings, J. B. Clendenning, R. J. Richter, G. P. Jarvik, and C. E. Furlong. 2001. Polymorphisms in the human paraoxonase (PON1) promoter. Pharmacogenetics 11:77-84.

     5.    Chan, H., D. P. Bartos, and L. B. Owen-Schaub. 1999. Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment. Mol Cell Biol. 19:2098-2108.

     6.    Chang, D. J., Y. K. Paik, T. P. Leren, D. W. Walker, G. J. Howlett, and J. M. Taylor. 1990. Characterization of a human apolipoprotein E gene enhancer element and its associated protein factors. J Biol. Chem. 265:9496-9504.

     7.    Chang, Y. J., M. J. Holtzman, and C. C. Chen. 2004. Differential role of Janus family kinases (JAKs) in interferon-gamma-induced lung epithelial ICAM-1 expression: involving protein interactions between JAKs, phospholipase Cgamma, c-Src, and STAT1. Mol Pharmacol 65:589-598.

     8.    Chen, C. C. and A. M. Manning. 1995. Transcriptional regulation of endothelial cell adhesion molecules: a dominant role for NF-kappa B. Agents Actions Suppl 47:135-141.

     9.    Chen, J., Y. Liu, H. Liu, P. L. Hermonat, and J. L. Mehta. 2006. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis. Biochem. J 393:255-265.

   10.    Chen, J., Y. Liu, H. Liu, P. L. Hermonat, and J. L. Mehta. 2006. Molecular dissection of angiotensin II-activated human LOX-1 promoter. Arterioscler. Thromb. Vasc. Biol. 26:1163-1168.

   11.    Chen, M., W. Li, N. Wang, Y. Zhu, and X. Wang. 2006. ROS and NF-{kappa}B but not LXR Mediate IL-1{beta} Signaling for the Downregulation of ATP-Binding Cassette Transporter A1. Am. J Physiol Cell Physiol.

   12.    Chen, Y. Q., M. Su, R. R. Walia, Q. Hao, J. W. Covington, and D. E. Vaughan. 1998. Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. J Biol. Chem. 273:8225-8231.

   13.    Chew, C. H., M. R. Samian, N. Najimudin, and T. S. Tengku-Muhammad. 2003. Molecular characterisation of six alternatively spliced variants and a novel promoter in human peroxisome proliferator-activated receptor alpha. Biochem. Biophys. Res. Commun. 305:235-243.

   14.    Cho, H. J., S. K. Kim, S. M. Jin, E. M. Hwang, Y. S. Kim, K. Huh, and I. Mook-Jung. 2007. IFN-gamma-induced BACE1 expression is mediated by activation of JAK2 and ERK1/2 signaling pathways and direct binding of STAT1 to BACE1 promoter in astrocytes. Glia 55:253-262.

   15.     Christensen, M. A., W. Zhou, H. Qing, A. Lehman, S. Philipsen, and W. Song. 2004. Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1. Mol Cell Biol. 24:865-874.

   16.    Cohen, I. R., S. Grassel, A. D. Murdoch, and R. V. Iozzo. 1993. Structural characterization of the complete human perlecan gene and its promoter. Proc. Natl. Acad. Sci. U. S. A  90:10404-10408.

   17.     Dabrowski, C. E., P. J. Carmillo, and P. A. Schaffer. 1994. Cellular protein interactions with herpes simplex virus type 1 oriS. Mol Cell Biol. 14:2545-2555.

   18.    Davis, M. E., I. M. Grumbach, T. Fukai, A. Cutchins, and D. G. Harrison. 2004. Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding. J Biol. Chem. 279:163-168.

   19.    Davis, W., Jr., Z. J. Chen, K. E. Ile, and K. D. Tew. 2003. Reciprocal regulation of expression of the human adenosine 5'-triphosphate binding cassette, sub-family A, transporter 2 (ABCA2) promoter by the early growth response-1 (EGR-1) and Sp-family transcription factors. Nucleic Acids Res. 31:1097-1107.

   20.     deGraffenried, L. A., S. G. Hilsenbeck, and S. A. Fuqua. 2002. Sp1 is essential for estrogen receptor alpha gene transcription. J Steroid Biochem. Mol Biol. 82:7-18.

   21.     deGraffenried, L. A., T. A. Hopp, A. J. Valente, R. A. Clark, and S. A. Fuqua. 2004. Regulation of the estrogen receptor alpha minimal promoter by Sp1, USF-1 and ERalpha. Breast Cancer Res. Treat. 85:111-120.

   22.    Demarchi, F., R. Verardo, B. Varnum, C. Brancolini, and C. Schneider. 2001. Gas6 anti-apoptotic signaling requires NF-kappa B activation. J Biol. Chem. 276:31738-31744.

   23.    Dimova, E. Y. and T. Kietzmann . 2006. Cell type-dependent regulation of the hypoxia-responsive plasminogen activator inhibitor-1 gene by upstream stimulatory factor-2. J Biol. Chem. 281:2999-3005.

   24.    Ding, Y., T. Inoue, J. Kamiyama, Y. Tamura, N. Ohtani-Fujita, E. Igata, and T. Sakai. 1999. Molecular cloning and functional characterization of the upstream promoter region of the human p73 gene. DNA Res. 6:347-351.

   25.    Douville, P., M. Hagmann, O. Georgiev, and W. Schaffner. 1995. Positive and negative regulation at the herpes simplex virus ICP4 and ICP0 TAATGARAT motifs. Virology 207:107-116.

   26.    Du, Y., X. Chen, X. Wei, K. R. Bales, D. T. Berg, S. M. Paul, M. R. Farlow, B. Maloney, Y. W. Ge, and D. K. Lahiri. 2005. NF-(kappa)B mediates amyloid beta peptide-stimulated activity of the human apolipoprotein E gene promoter in human astroglial cells. Brain Res. Mol Brain Res. 136:177-188.

   27.    Eyries, M., M. Agrapart, A. Alonso, and F. Soubrier. 2002. Phorbol ester induction of angiotensin-converting enzyme transcription is mediated by Egr-1 and AP-1 in human endothelial cells via ERK1/2 pathway. Circ. Res. 91:899-906.

   28.    Fan, W., T. Yanase, H. Morinaga, Y. M. Mu, M. Nomura, T. Okabe, K. Goto, N. Harada, and H. Nawata. 2005. Activation of peroxisome proliferator-activated receptor-gamma and retinoid X receptor inhibits aromatase transcription via nuclear factor-kappaB. Endocrinology 146:85-92.

   29.     Feigenbaum, A. S. and B. H. Robinson. 1993. The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Genomics 17:376-381.

   30.    Feldman, G. M., E. J. Chuang, and D. S. Finbloom. 1995. IgG immune complexes inhibit IFN-gamma-induced transcription of the Fc gamma RI gene in human monocytes by preventing the tyrosine phosphorylation of the p91 (Stat1) transcription factor. J Immunol. 154:318-325.

   31.    Fornasari, D., E. Battaglioli, A. Flora, S. Terzano, and F. Clementi. 1997. Structural and functional characterization of the human alpha3 nicotinic subunit gene promoter. Mol Pharmacol 51:250-261.

   32.    Fujiwara, J., M. Fujii, M. Shimoda, and D. Ayusawa. 2000. Identification of the UV-responsive sequence in the human tissue plasminogen activator gene. Biosci. Biotechnol. Biochem. 64:1084-1087.

   33.    Gabay, C., M. F. Smith, D. Eidlen, and W. P. Arend. 1997. Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein. J Clin. Invest 99:2930-2940.

   34.    Garban, H. J. and B. Bonavida. 2001. Nitric oxide inhibits the transcription repressor Yin-Yang 1 binding activity at the silencer region of the Fas promoter: a pivotal role for nitric oxide in the up-regulation of Fas gene expression in human tumor cells. J Immunol. 167:75-81.

   35.    Gauthier, B., M. Robb, F. Gaudet, G. S. Ginsburg, and R. McPherson. 1999. Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1. J Lipid Res. 40:1284-1293.

   36.    Ghozi, M. C., Y. Bernstein, V. Negreanu, D. Levanon, and Y. Groner. 1996. Expression of the human acute myeloid leukemia gene AML1 is regulated by two promoter regions. Proc. Natl. Acad. Sci. U. S. A 93:1935-1940.

   37.    Grilli, M., F. Goffi, M. Memo, and P. Spano. 1996. Interleukin-1beta and glutamate activate the NF-kappaB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures. J Biol. Chem. 271:15002-15007.

   38.    Gu, W., Q. Huang, and G. S. Hayward. 1995. Multiple Tandemly Repeated Binding Sites for the YY1 Repressor and Transcription Factors AP-1 and SP-1 Are Clustered within Intron-1 of the Gene Encoding the IE110 Transactivator of Herpes simplex Virus Type 1. J Biomed. Sci. 2:203-226.

   39.    Gunther, M., M. Laithier, and O. Brison. 2000. A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening. Mol Cell Biochem. 210:131-142.

   40.    Guo, J., V. Casolaro, E. Seto, W. M. Yang, C. Chang, M. C. Seminario, J. Keen, and S. N. Georas. 2001. Yin-Yang 1 activates interleukin-4 gene expression in T cells. J Biol. Chem. 276:48871-48878.

   41.    Haas, M. J., M. H. Horani, N. C. Wong, and A. D. Mooradian. 2004. Induction of the apolipoprotein AI promoter by Sp1 is repressed by saturated fatty acids. Metabolism 53:1342-1348.

   42.    Hansen, S. K., C. Nerlov, U. Zabel, P. Verde, M. Johnsen, P. A. Baeuerle, and F. Blasi. 1992. A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene. EMBO J  11:205-213.

   43.    Hargett, D., S. Rice, and S. L. Bachenheimer. 2006. Herpes simplex virus type 1 ICP27-dependent activation of NF-kappaB. J Virol. 80:10565-10578.

   44.    Heicklen-Klein, A. and I. Ginzburg. 2000. Tau promoter confers neuronal specificity and binds Sp1 and AP-2. Journal of Neurochemistry. 75:1408-1418.

   45.    Heils, A., A. Teufel, S. Petri, M. Seemann, D. Bengel, U. Balling, P. Riederer, and K. P. Lesch. 1995. Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm. Gen. Sect. 102:247-254.

   46.    Hiscott, J., J. Marois, J. Garoufalis, M. D'Addario, A. Roulston, I. Kwan, N. Pepin, J. Lacoste, H. Nguyen, G. Bensi, and . 1993. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol. 13:6231-6240.

   47.    Hohjoh, H. and K. Tokunaga. 2001. Allele-specific binding of the ubiquitous transcription factor OCT-1 to the functional single nucleotide polymorphism (SNP) sites in the tumor necrosis factor-alpha gene (TNFA) promoter. Genes Immun. 2:105-109.

   48.     Homberger, A., M. Linnebank, C. Winter, H. Willenbring, T. Marquardt, E. Harms, and H. G. Koch. 2000. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur. J Hum. Genet. 8:725-729.

   49.    Hu, Q., W. A. Kukull, S. L. Bressler, M. D. Gray, J. A. Cam, E. B. Larson, G. M. Martin, and S. S. Deeb. 1998. The human FE65 gene: genomic structure and an intronic biallelic polymorphism associated with sporadic dementia of the Alzheimer type. Hum. Genet. 103:295-303.

   50.    Husmann, M., P. Jehnichen, B. Jahn, D. Schlosshan, E. Romahn, and J. Marx. 1996. A novel SP-1 site in the human interleukin-1 beta promoter confers preferential transcriptional activity in keratinocytes. Eur. J Immunol. 26:3008-3014.

   51.    Ibanez-Tallon, I., C. Ferrai, E. Longobardi, I. Facetti, F. Blasi, and M. P. Crippa. 2002. Binding of Sp1 to the proximal promoter links constitutive expression of the human uPA gene and invasive potential of PC3 cells. Blood 100:3325-3332.

   52.    Inoue, H., E. E. Baetge, and L. B. Hersh. 1993. Enhancer containing unusual GC box-like sequences on the human choline acetyltransferase gene. Brain Res. Mol Brain Res. 20:299-304.

   53.    Jbilo, O., J. P. Toutant, K. P. Vatsis, A. Chatonnet, and O. Lockridge. 1994. Promoter and transcription start site of human and rabbit butyrylcholinesterase genes. J Biol. Chem. 269:20829-20837.

   54.    Jiang, B. and C. R. Mendelson. 2005. O2 enhancement of human trophoblast differentiation and hCYP19 (aromatase) gene expression are mediated by proteasomal degradation of USF1 and USF2. Mol Cell Biol. 25:8824-8833.

   55.    Joo, M., J. G. Wright, N. N. Hu, R. Sadikot, G. Y. Park, T. S. Blackwell, and J. W. Christman. 2007. Yin Yang 1 enhances cyclooxygenase-2 gene expression in macrophages. Am. J Physiol Lung Cell Mol Physiol.

   56.     Kaltschmidt, B., P. A. Baeuerle, and C. Kaltschmidt. 1993. Potential involvement of the transcription factor NF-kappa B in neurological disorders. Mol Aspects Med 14:171-190.

   57.     Kanemitsu, S., K. Ihara, A. Saifddin, T. Otsuka, T. Takeuchi, J. Nagayama, M. Kuwano, and T. Hara. 2002. A functional polymorphism in fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus. J Rheumatol. 29:1183-1188.

   58.    Kang, H. C., B. M. Chung, J. H. Chae, S. I. Yang, C. G. Kim, and C. G. Kim. 2005. Identification and characterization of four novel peptide motifs that recognize distinct regions of the transcription factor CP2. FEBS J 272:1265-1277.

   59.    Kantarci, O. H., E. J. Atkinson, D. D. Hebrink, C. T. McMurray, and B. G. Weinshenker. 2000. Association of a myeloperoxidase promoter polymorphism with multiple sclerosis. J. Neuroimmunol. 105:189-194.

   60.     Karantzoulis-Fegaras, F., H. Antoniou, S. L. Lai, G. Kulkarni, C. D'Abreo, G. K. Wong, T. L. Miller, Y. Chan, J. Atkins, Y. Wang, and P. A. Marsden. 1999. Characterization of the human endothelial nitric-oxide synthase promoter. J Biol. Chem. 274:3076-3093.

   61.    Kardassis, D., E. Falvey, P. Tsantili, M. Hadzopoulou-Cladaras, and V. Zannis. 2002. Direct physical interactions between HNF-4 and Sp1 mediate synergistic transactivation of the apolipoprotein CIII promoter. Biochemistry 41:1217-1228.

   62.    Kenny, J. J., S. Millhouse, M. Wotring, and B. Wigdahl. 1997. Upstream stimulatory factor family binds to the herpes simplex virus type 1 latency-associated transcript promoter. Virology 230:381-391.

   63.    Kim, D. B. and N. A. DeLuca. 2002. Phosphorylation of transcription factor Sp1 during herpes simplex virus type 1 infection. J Virol. 76:6473-6479.

   64.    Kim, S. J., A. Glick, M. B. Sporn, and A. B. Roberts. 1989. Characterization of the promoter region of the human transforming growth factor-beta 1 gene. J Biol. Chem. 264:402-408.

   65.    Kreysing, J., K. von Figura, and V. Gieselmann. 1990. Structure of the arylsulfatase A gene. Eur. J Biochem. 191:627-631.

   66.    Kriesel, J. D., B. B. Jones, K. M. Dahms, and S. L. Spruance. 2004. STAT1 binds to the herpes simplex virus type 1 latency-associated transcript promoter. J Neurovirol. 10:12-20.

   67.    Kunz, M., G. Bloss, R. Gillitzer, G. Gross, M. Goebeler, U. R. Rapp, and S. Ludwig. 2002. Hypoxia/reoxygenation induction of monocyte chemoattractant protein-1 in melanoma cells: involvement of nuclear factor-kappaB, stimulatory protein-1 transcription factors and mitogen-activated protein kinase pathways. Biochem. J 366:299-306.

   68.    Lahiri, D. K. 2004. Apolipoprotein E as a target for developing new therapeutics for Alzheimer's disease based on studies from protein, RNA, and regulatory region of the gene. J Mol Neurosci 23:225-233.

   69.    Lahiri, D. K., Y. W. Ge, J. T. Rogers, K. Sambamurti, N. H. Greig, and B. Maloney. 2006. Taking down the unindicted co-conspirators of amyloid beta-peptide-mediated neuronal death: shared gene regulation of BACE1 and APP genes interacting with CREB, Fe65 and YY1 transcription factors. Curr. Alzheimer Res. 3:475-483.

   70.     Lambertini, E., L. Penolazzi, S. Giordano, L. Del Senno, and R. Piva. 2003. Expression of the human oestrogen receptor-alpha gene is regulated by promoter F in MG-63 osteoblastic cells. Biochem. J 372:831-839.

   71.    Lau, K. F., C. C. Miller, B. H. Anderton, and P. C. Shaw. 1999. Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter. Genomics 60:121-128.

   72.    Leclerc, D., M. Odievre, Q. Wu, A. Wilson, J. J. Huizenga, R. Rozen, S. W. Scherer, and R. A. Gravel. 1999. Molecular cloning, expression and physical mapping of the human methionine synthase reductase gene. Gene 240:75-88.

   73.    Lee, K. Y., K. Ito, R. Hayashi, E. P. Jazrawi, P. J. Barnes, and I. M. Adcock. 2006. NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-beta1 gene transcription. J Immunol. 176:603-615.

   74.    Lee, P. L., C. Halloran, and E. Beutler. 2001. Polymorphisms in the transferrin 5' flanking region associated with differences in total iron binding capacity: possible implications in iron homeostasis. Blood Cells Mol. Dis. 27:539-548.

   75.    Lieu, P. T. and E. K. Wagner. 2000. Two leaky-late HSV-1 promoters differ significantly in structural architecture. Virology 272:191-203.

   76.    Lomonte, P., J. Thomas, P. Texier, C. Caron, S. Khochbin, and A. L. Epstein. 2004. Functional interaction between class II histone deacetylases and ICP0 of herpes simplex virus type 1. J Virol. 78:6744-6757.

   77.    Mahajan, S. S., M. M. Little, R. Vazquez, and A. C. Wilson. 2002. Interaction of HCF-1 with a cellular nuclear export factor. J Biol. Chem. 277:44292-44299.

   78.    Mahal, S. P., E. A. Asante, M. Antoniou, and J. Collinge. 2001. Isolation and functional characterisation of the promoter region of the human prion protein gene. Gene 268:105-114.

   79.    Maloney, B., Y. W. Ge, N. H. Greig, and D. K. Lahiri. 2006. Characterization of the human beta-secretase 2 (BACE2) 5'-Flanking region: identification of a 268-bp region as the basal BACE2 promoter. J Mol Neurosci 29:81-99.

   80.     Matsusaka, T., K. Fujikawa, Y. Nishio, N. Mukaida, K. Matsushima, T. Kishimoto, and S. Akira. 1993. Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc. Natl. Acad. Sci. U. S. A 90:10193-10197.

   81.    McDowell, T. L., J. A. Symons, and G. W. Duff. 2005. Human interleukin-1 alpha gene expression is regulated by Sp1 and a transcriptional repressor. Cytokine 30:141-153.

   82.    Mills, L. K., Y. Shi, and R. L. Millette. 1994. YY1 is the cellular factor shown previously to bind to regulatory regions of several leaky-late (beta gamma, gamma 1) genes of herpes simplex virus type 1. J Virol. 68:1234-1238.

   83.    Mura, C., G. Le Gac, S. Jacolot, and C. Ferec. 2004. Transcriptional regulation of the human HFE gene indicates high liver expression and erythropoiesis coregulation. FASEB J 18:1922-1924.

   84.    Nackley, A. C., W. Shea-Eaton, D. Lopez, and M. P. McLean. 2002. Repression of the steroidogenic acute regulatory gene by the multifunctional transcription factor Yin Yang 1. Endocrinology 143:1085-1096.

   85.    Nakano, K., C. Takase, T. Sakamoto, S. Nakagawa, J. Inazawa, S. Ohta, and S. Matuda. 1994. Isolation, characterization and structural organization of the gene and pseudogene for the dihydrolipoamide succinyltransferase component of the human 2-oxoglutarate dehydrogenase complex. Eur. J Biochem. 224:179-189.

   86.     Nathanson, C. M., J. Wasselius, H. Wallin, and M. Abrahamson. 2002. Regulated expression and intracellular localization of cystatin F in human U937 cells. Eur. J Biochem. 269:5502-5511.

   87.    North, S., X. Espanel, F. Bantignies, B. Viollet, V. Vallet, P. Jalinot, G. Brun, and G. Gillet. 1999. Regulation of cdc2 gene expression by the upstream stimulatory factors (USFs). Oncogene 18:1945-1955.

   88.    Oei, S. L., J. Griesenbeck, M. Schweiger, V. Babich, A. Kropotov, and N. Tomilin. 1997. Interaction of the transcription factor YY1 with human poly(ADP-ribosyl) transferase. Biochem. Biophys. Res. Commun. 240:108-111.

   89.    Okawa, Y., A. Adachi, M. Ino, S. Nagumo, and H. Matsui. 1998. Further characterization of the 5'-flanking promoter region of the human beta1-adrenergic receptor gene. Psychiatry Clin. Neurosci 52:453-458.

   90.    Ou, X. M., K. Chen, and J. C. Shih. 2006. Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1. J Biol. Chem. 281:21512-21525.

   91.    Pastier, D., J. M. Lacorte, J. Chambaz, P. Cardot, and A. Ribeiro. 2002. Two initiator-like elements are required for the combined activation of the human apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear factor-4. J Biol. Chem. 277:15199-15206.

   92.    Pastorcic, M. and H. K. Das. 1999. An upstream element containing an ETS binding site is crucial for transcription of the human presenilin-1 gene. J Biol. Chem. 274 :24297-24307.

   93.    Pastorcic, M. and H. K. Das. 2003. Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter. Brain Res. Mol Brain Res. 113:57-66.

   94.    Payson, R. A., M. A. Chotani, and I. M. Chiu. 1998. Regulation of a promoter of the fibroblast growth factor 1 gene in prostate and breast cancer cells. J Steroid Biochem. Mol Biol. 66:93-103.

   95.    Pollwein, P. 1993. Overlapping binding sites of two different transcription factors in the promoter of the human gene for the Alzheimer amyloid precursor protein. Biochem. Biophys. Res. Commun. 190:637-647.

   96.    Prasad, P. D., H. W. Li, Y. J. Fei, M. E. Ganapathy, T. Fujita, L. H. Plumley, T. L. Yang-Feng, F. H. Leibach, and V. Ganapathy. 1998. Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene. Journal of Neurochemistry. 70:443-451.

   97.    Previato, L., C. L. Parrott, S. Santamarina-Fojo, and H. B. Brewer, Jr. 1991. Transcriptional regulation of the human lipoprotein lipase gene in 3T3-L1 adipocytes. J Biol. Chem. 266:18958-18963.

   98.    Redecker, B., B. Heckendorf, H. W. Grosch, G. Mersmann, and A. Hasilik. 1991. Molecular organization of the human cathepsin D gene. DNA Cell Biol. 10:423-431.

   99.    Renbaum, P., R. Beeri, E. Gabai, M. Amiel, M. Gal, M. U. Ehrengruber, and E. Levy-Lahad. 2003. Egr-1 upregulates the Alzheimer's disease presenilin-2 gene in neuronal cells. Gene 318:113-24.:113-124.

100.    Rossner, S., M. Sastre, K. Bourne, and S. F. Lichtenthaler. 2006. Transcriptional and translational regulation of BACE1 expression--implications for Alzheimer's disease. Prog. Neurobiol. 79:95-111.

101.    Salero, E., C. Gimenez, and F. Zafra. 2003. Identification of a non-canonical E-box motif as a regulatory element in the proximal promoter region of the apolipoprotein E gene. Biochem. J 370:979-986.

102.    Sanceau, J., T. Kaisho, T. Hirano, and J. Wietzerbin. 1995. Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1, NF kappa B, and Sp1 transcription factors. J Biol. Chem. 270:27920-27931.

103.    Sato, H., A. Watanabe, T. Tanaka, N. Koitabashi, M. Arai, M. Kurabayashi, and T. Yokoyama. 2003. Regulation of the human tumor necrosis factor-alpha promoter by angiotensin II and lipopolysaccharide in cardiac fibroblasts: different cis-acting promoter sequences and transcriptional factors. J. Mol. Cell Cardiol. 35:1197-1205.

104.    Saur, D., B. Seidler, H. Paehge, V. Schusdziarra, and H. D. Allescher. 2002. Complex regulation of human neuronal nitric-oxide synthase exon 1c gene transcription. Essential role of Sp and ZNF family members of transcription factors. J Biol. Chem. 277:25798-25814.

105.    Schmedtje, J. F., Jr., Y. S. Ji, W. L. Liu, R. N. DuBois, and M. S. Runge. 1997. Hypoxia induces cyclooxygenase-2 via the NF-kappaB p65 transcription factor in human vascular endothelial cells. J Biol. Chem. 272:601-608.

106.    Schmitz, G. and T. Langmann. 2005. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim. Biophys. Acta 1735:1-19.

107.    Sezaki, N., F. Ishimaru, T. Tabayashi, I. Kataoka, K. Nakase, K. Fujii, T. Kozuka, H. Nakayama, M. Harada, and M. Tanimoto. 2003. The type 1 CD10/neutral endopeptidase 24.11 promoter: functional characterization of the 5'-untranslated region. Br. J Haematol. 123:177-183.

108.    Song, C. S., M. H. Jung, P. C. Supakar, S. Chen, R. L. Vellanoweth, B. Chatterjee, and A. K. Roy. 1995. Regulation of androgen action by receptor gene inhibition. Ann. N. Y. Acad. Sci. 761:97-108.

109.    Song, J., H. Ugai, H. Nakata-Tsutsui, S. Kishikawa, E. Suzuki, T. Murata, and K. K. Yokoyama. 2003. Transcriptional regulation by zinc-finger proteins Sp1 and MAZ involves interactions with the same cis-elements. Int. J Mol Med 11:547-553.

110.    Stewart, M. J., K. M. Dipple, T. R. Stewart, and D. W. Crabb. 1996. The role of nuclear factor NF-Y/CP1 in the transcriptional regulation of the human aldehyde dehydrogenase 2-encoding gene. Gene 173:155-161.

111.    Thompson, J. F., D. B. Lloyd, M. E. Lira, and P. M. Milos. 2004. Cholesteryl ester transfer protein promoter single-nucleotide polymorphisms in Sp1-binding sites affect transcription and are associated with high-density lipoprotein cholesterol. Clin. Genet. 66:223-228.

112.    Tilley, W. D., M. Marcelli, and M. J. McPhaul. 1990. Expression of the human androgen receptor gene utilizes a common promoter in diverse human tissues and cell lines. J Biol. Chem. 265:13776-13781.

113.    Tischer, E., R. Mitchell, T. Hartman, M. Silva, D. Gospodarowicz, J. C. Fiddes, and J. A. Abraham. 1991. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol. Chem. 266:11947-11954.

114.    Tominaga, K., S. Akiyama, Y. Kagawa, and S. Ohta. 1992. Upstream region of a genomic gene for human mitochondrial transcription factor 1. Biochim. Biophys. Acta 1131:217-219.

115.    Tommasi, S. and G. P. Pfeifer . 1995. In vivo structure of the human cdc2 promoter: release of a p130-E2F-4 complex from sequences immediately upstream of the transcription initiation site coincides with induction of cdc2 expression. Mol Cell Biol. 15:6901-6913.

116.    Ueda, A., K. Okuda, S. Ohno, A. Shirai, T. Igarashi, K. Matsunaga, J. Fukushima, S. Kawamoto, Y. Ishigatsubo, and T. Okubo. 1994. NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. J Immunol. 153:2052-2063.

117.    Ulrich, C. M., J. Whitton, J. H. Yu, J. Sibert, R. Sparks, J. D. Potter, and J. Bigler. 2005. PTGS2 (COX-2) -765G > C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol. Biomarkers Prev. 14:616-619.

118.    Vaishnaw, A. K., T. J. Mitchell, S. J. Rose, M. J. Walport, and B. J. Morley. 1998. Regulation of transcription of the TATA-less human complement component C4 gene. J Immunol.  160:4353-4360.

119.    Valente, A. J., J. F. Xie, M. A. Abramova, U. O. Wenzel, H. E. Abboud, and D. T. Graves. 1998. A complex element regulates IFN-gamma-stimulated monocyte chemoattractant protein-1 gene transcription. J Immunol. 161:3719-3728.

120.    Virbasius, J. V. and R. C. Scarpulla. 1994. Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc. Natl. Acad. Sci. U. S. A 91:1309-1313.

121.    Voleti, B. and A. Agrawal. 2005. Regulation of basal and induced expression of C-reactive protein through an overlapping element for OCT-1 and NF-kappaB on the proximal promoter. J Immunol. 175:3386-3390.

122.    Vostrov, A. A., W. W. Quitschke, F. Vidal, A. L. Schwarzman, and D. Goldgaber. 1995. USF binds to the APB alpha sequence in the promoter of the amyloid beta-protein precursor gene. Nucleic Acids Res. 23:2734-2741.

123.    Wang, F., I. Samudio, and S. Safe. 2001. Transcriptional activation of cathepsin D gene expression by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition. Mol Cell Endocrinol. 172:91-103.

124.    Weigert, C., K. Brodbeck, M. Sawadogo, H. U. Haring, and E. D. Schleicher. 2004. Upstream stimulatory factor (USF) proteins induce human TGF-beta1 gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. J Biol. Chem. 279:15908-15915.

125.    Wysocka, J. and W. Herr. 2003. The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem. Sci. 28:294-304.

126.    Yamamoto, K., H. Takeshima, K. Hamada, M. Nakao, T. Kino, T. Nishi, M. Kochi, J. Kuratsu, T. Yoshimura, and Y. Ushio. 1999. Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5'-untranslated region in tissue-specific expression. J Biol. Chem. 274:4646-4654.

127.    Yang, J. B., Z. J. Duan, W. Yao, O. Lee, L. Yang, X. Y. Yang, X. Sun, C. C. Chang, T. Y. Chang, and B. L. Li. 2001. Synergistic transcriptional activation of human Acyl-coenzyme A: cholesterol acyltransterase-1 gene by interferon-gamma and all-trans-retinoic acid THP-1 cells. J Biol. Chem. 276:20989-20998.

128.    Yang, W. S. and S. S. Deeb. 1998. Sp1 and Sp3 transactivate the human lipoprotein lipase gene promoter through binding to a CT element: synergy with the sterol regulatory element binding protein and reduced transactivation of a naturally occurring promoter variant. J Lipid Res. 39:2054-2064.

129.    Yang, X. P., L. A. Freeman, C. L. Knapper, M. J. Amar, A. Remaley, H. B. Brewer, Jr., and S. Santamarina-Fojo . 2002. The E-box motif in the proximal ABCA1 promoter mediates transcriptional repression of the ABCA1 gene. J Lipid Res. 43:297-306.

130.    Yang, X. P., K. Irani, S. Mattagajasingh, A. Dipaula, F. Khanday, M. Ozaki, K. Fox-Talbot, W. M. Baldwin, III, and L. C. Becker. 2005. Signal transducer and activator of transcription 3alpha and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium. Arterioscler. Thromb. Vasc. Biol. 25:1395-1400.

131.    Yoshioka, H., P. Greenwel, K. Inoguchi, S. Truter, Y. Inagaki, Y. Ninomiya, and F. Ramirez. 1995. Structural and functional analysis of the promoter of the human alpha 1(XI) collagen gene. J Biol. Chem. 270:418-424.

132.    Zaniolo, K., A. Rufiange, S. Leclerc, S. Desnoyers, and S. L. Guerin. 2005. Regulation of the poly(ADP-ribose) polymerase-1 gene expression by the transcription factors Sp1 and Sp3 is under the influence of cell density in primary cultured cells. Biochem. J 389:423-433.

133.    Zhao, Q. and F. S. Lee. 2003. The transcriptional activity of the APP intracellular domain-Fe65 complex is inhibited by activation of the NF-kappaB pathway. Biochemistry 42:3627-3634.

134.    Zhao, Y., C. R. Mendelson, and E. R. Simpson. 1995. Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes. Mol Endocrinol. 9:340-349.