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Promoter Microsatellites as Modulators of Human Gene Expression

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Tandem Repeat Polymorphisms

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB))

Abstract

Microsatellites in and around genes have been shown to modulate levels of gene expression in multiple organisms, ranging from bacteria to humans. Here we will discuss promoter microsatellites known to modulate gene expression, with a few key examples related to the human brain. Many of the micro satellites we discuss are highly conserved in mammals, indicating that selection may favor their retention as “tuning knobs” of gene expression. We will also discuss the mechanisms by which microsatellites in promoters can alter gene expression as they expand and contract, with particular attention to secondary structures like Z-DNA and H-DNA. We suggest that promoter microsatellites, especially those that are highly conserved, may be an important source of human phenotypic variation.

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References

  1. Toth G, Gaspari Z, Jurka J. Microsatellites in different eukaryotic genomes: survey and analysis. Genome Res 2000; 10:967–981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Moxon R, Bayliss C, Hood D. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet 2006; 40:307–333.

    Article  CAS  PubMed  Google Scholar 

  3. Wang G, Vasquez KM. Z-DNA, an active element in the genome. Front Biosci 2007; 12:4424–4438.

    Article  CAS  PubMed  Google Scholar 

  4. Kouzine F, Sanford S, Elisha-Feil Z et al. The functional response of upstream DNA to dynamic supercoiling in vivo. Nat Struct Mol Biol 2008; 15:146–154.

    Article  CAS  PubMed  Google Scholar 

  5. Martin P, Makepeace K, Hill SA et al. Microsatellite instability regulates transcription factor binding and gene expression. Proc Natl Acad Sci U S A 2005; 102:3800–3804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sarkari J, Pandit N, Moxon ER et al. Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine. Mol Microbiol 1994; 13:207–217.

    Article  CAS  PubMed  Google Scholar 

  7. Sawaya R, Arhin FF, Moreau F et al. Mutational analysis of the promoter region of the porA gene of Neisseria meningitidis. Gene 1999; 233:49–57.

    Article  CAS  PubMed  Google Scholar 

  8. Carson SD, Stone B, Beucher M et al. Phase variation of the gonococcal siderophore receptor FetA. Mol Microbiol 2000; 36:585–593.

    Article  CAS  PubMed  Google Scholar 

  9. Vinces MD, Legendre M, Caldara M et al. Unstable tandem repeats in promoters confer transcriptional evolvability. Science 2009; 324:1213–1216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Iyer V, Struhl K. Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. EMBO J 1995; 14:2570–2579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kirkpatrick DT, Wang YH, Dominska M et al. Control of meiotic recombination and gene expression in yeast by a simple repetitive DNA sequence that excludes nucleosomes. Mol Cell Biol 1999; 19:7661–7671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hammock EA, Young LJ. Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 2005; 308:1630–1634.

    Article  CAS  PubMed  Google Scholar 

  13. Walum H, Westberg L, Henningsson S et al. Genetic variation in the vasopressinreceptorlagene(AVPRlA) associates with pair-bonding behavior in humans. Proc Natl Acad Sci U S A 2008; 105:14153–14156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Knafo A, Israel S, Darvasi A et al. Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin la receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA. Genes Brain Behav 2008; 7:266–275.

    Article  CAS  PubMed  Google Scholar 

  15. Meyer-Lindenberg A, Kolachana B, Gold B et al. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry 2009; 14:968–975.

    Article  CAS  PubMed  Google Scholar 

  16. Bachner-Melman R, Dina C, Zohar AH et al. AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance. PLoS Genet 2005; 1:e42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Ukkola LT, Onkamo P, Raijas P et al. Musical aptitude is associated with AVPRlA-haplotypes. PLoS ONE 2009; 4:e5534.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Rothenburg S, Koch-Nolte F, Rich A et al. A polymorphic dinucleotide repeat in the rat nucleolin gene forms Z-DNA and inhibits promoter activity. Proc Natl Acad Sci U S A 2001; 98:8985–8990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hayes TE, Dixon JE. Z-DNA in the rat somatostatin gene. J Biol Chem 1985; 260:8145–8156.

    CAS  PubMed  Google Scholar 

  20. Thomas MJ, Freeland TM, Strobl JS. Z-DNA formation in the rat growth hormone gene promoter region. Mol Cell Biol 1990; 10:5378–5387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Naylor LH, Clark EM. d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription. Nucleic Acids Res 1990; 18:1595–1601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rockman M, Wray G, Wray G. Abundant raw material for cis-regulatory evolution in humans. Molecular Biology and Evolution 2002; 19:1991–2004.

    Article  CAS  PubMed  Google Scholar 

  23. Rothenburg S, Koch-Nolte F, Haag F. DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles. Immunol Rev 2001; 184:286–298.

    Article  CAS  PubMed  Google Scholar 

  24. Streelman JT, Kocher TD. Microsatellite variation associated with prolactin expression and growth of salt challenged tilapia. Physiol Genomics 2002; 9:1–4.

    Article  CAS  PubMed  Google Scholar 

  25. Xu G, Goodridge AG. A CT repeat in the promoter of the chicken malic enzyme gene is essential for function at an alternative transcription start site. Arch Biochem Biophys 1998; 358:83–91.

    Article  CAS  PubMed  Google Scholar 

  26. Sawaya S, Lennon D, Buschiazzo E et al. Measuring microsatellite conservation in mammals with a phylogenetic birth death model. Submitted to Gen Biol and Evol 2011.

    Google Scholar 

  27. Chen YH, Lin SJ, Lin MW et al. Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients. Hum Genet 2002; 111:18.

    Article  CAS  Google Scholar 

  28. Contente A, Dittmer A, Koch MC et al. A polymorphic microsatellite that mediates induction of PIG3 by p53. Nat Genet 2002; 30:315–320.

    Article  PubMed  Google Scholar 

  29. Rife T, Rasoul B, Pullen N et al. The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson’s disease. J Neurosci Res 2009; 87:2319–2325.

    Article  CAS  PubMed  Google Scholar 

  30. Reif A, Jacob CP, Rujescu D et al. Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Arch Gen Psychiatry 2009; 66:41–50.

    Article  CAS  PubMed  Google Scholar 

  31. Ng TK, Lam CY, Lam DS et al. AC and AG dinucleotide repeats in the pax6 P1 promoter are associated with high myopia. Mol Vis 2009; 15:2239–2248.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Albanese V, Biguet NF, Kiefer H et al. Quantitative effects on gene silencing by allelic variation at a tetranucleotide microsatellite. Hum Mol Genet 2001; 10:1785–1792.

    Article  CAS  PubMed  Google Scholar 

  33. Gao PS, Heller NM, Walker W et al. Variation in dinucleotide (GT) repeat sequence in the first exon of the STAT6 gene is associated with atopic asthma and differentially regulates the promoter activity in vitro. J Med Genet 2004; 41:535–539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yim JJ, Lee HW, Lee HS et al. The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun 2006; 7:150–155.

    Article  CAS  PubMed  Google Scholar 

  35. Agarwal AK, Giacchetti G, Lavery G et al. CA-Repeat polymorphism in intron 1 of HSD11B2: effects on gene expression and salt sensitivity. Hypertension 2000; 36:187–194.

    Article  CAS  PubMed  Google Scholar 

  36. Akai J, Kimura A, Hata RI. Transcriptional regulation of the human type I collagen alpha2 (COL1A2) gene by the combination of two dinucleotide repeats. Gene 1999; 239:65–73.

    Article  CAS  PubMed  Google Scholar 

  37. Itokawa M, Yamada K, Yoshitsugu K et al. Amicrosatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia. Pharmacogenetics 2003; 13:271–278.

    Article  CAS  PubMed  Google Scholar 

  38. Searle S, Blackwell JM. Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility. J Med Genet 1999; 36:295–299.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Yamada N, Yamaya M, Okinaga S et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet 2000; 66:187–195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shimajiri S, Arima N, Tanimoto A et al. Shortened microsatellite d(CA)21 sequence down-regulates promoter activity of matrix metalloproteinase 9 gene. FEBS Lett 1999; 455:70–74.

    Article  CAS  PubMed  Google Scholar 

  41. Okladnova O, Syagailo YV, Tranitz M et al. A promoter-associated polymorphic repeat modulates PAX-6 expression in human brain. Biochem Biophys Res Commun 1998; 248:402–405.

    Article  CAS  PubMed  Google Scholar 

  42. Okladnova O, Syagailo YV, Tranitz M et al. Functional characterization of the human PAX3 gene regulatory region. Genomics 1999; 57:110–119.

    Article  CAS  PubMed  Google Scholar 

  43. Hough C, Cameron CL, Notley CR et al. Influence of a GT repeat element on shear stress responsiveness of the VWF gene promoter. J Thromb Haemost 2008; 6:1183–1190.

    Article  CAS  PubMed  Google Scholar 

  44. Wang B, Ren J, Ooi LL et al. Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients. Oncogene 2005; 24:3999–4008.

    Article  CAS  PubMed  Google Scholar 

  45. Roberts RL, Gearry RB, Bland MV et al. Trinucleotide repeat variants in the promoter of the thiopurine S-methyltransferase gene of patients exhibiting ultra-high enzyme activity. Pharmacogenet Genomics 2008; 18:434–438.

    Article  CAS  PubMed  Google Scholar 

  46. Vedrine SM, Vourc-h P, Tabagh R et al. A functional tetranucleotide (AAAT) polymorphism in an Alu element in the NF1 gene is associated with mental retardation. Neurosci Lett 2011; 491:118–121.

    Article  CAS  PubMed  Google Scholar 

  47. Valverde P, Koren G. Purification and preliminary characterization of a cardiac Kv1.5 repressor element binding factor. Circ Res 1999; 84:937–944.

    Article  CAS  PubMed  Google Scholar 

  48. Gebhardt F, Zanker KS, Brandt B. Modulation of epidermal growth factor receptor gene transcription by apolymorphic dinucleotide repeat in intron 1. J Biol Chem 1999; 274:13176–13180.

    Article  CAS  PubMed  Google Scholar 

  49. Funke-Kaiser H, Thomas A, Bremer J et al. Regulation of the major isoform of human endothelin-converting enzyme-1 by a strong housekeeping promoter modulated by polymorphic microsatellites. J Hypertens 2003; 21:2111–2124.

    Article  CAS  PubMed  Google Scholar 

  50. Stuehr DJ. Mammalian nitric oxide synthases. Biochim Biophys Acta 1999; 1411:217–230.

    Article  CAS  PubMed  Google Scholar 

  51. Reif A, Kiive E, Kurrikof T et al. A functional pax6 promoter polymorphism interacts with adverse environment onfunctional and dysfunctional impulsivity. Psychopharmacology(Berl.)2011; 214:239–248.

    Article  CAS  Google Scholar 

  52. Retz W, Reif A, Freitag CM et al. Association of a functional variant of neuronal nitric oxide synthase gene with self-reported impulsiveness, venturesomeness and empathy in male offenders. JNeural Transm 2010; 117:321–324.

    Article  CAS  Google Scholar 

  53. Laas K, Reif A, Herterich S et al. The effect of a functional pax6 promoter polymorphism on impulsivity is moderated by platelet MAO activity. Psychopharmacology (Berl.) 2010; 209:255–261.

    Article  CAS  Google Scholar 

  54. Nelson RJ, Demas GE, Huang PL et al. Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 1995; 378:383–386.

    Article  CAS  PubMed  Google Scholar 

  55. Kelkar YD, Tyekucheva S, Chiaromonte F et al. The genome-wide determinants of human and chimpanzee microsatellite evolution. Genome Res 2008; 18:30–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Grindley JC, Davidson DR, Hill RE. The role of Pax-6 in eye and nasal development. Development 1995; 121:1433–1442.

    CAS  PubMed  Google Scholar 

  57. Larsen KB, Lutterodt MC, Laursen H et al. Spatiotemporal distribution of pax6 and MEIS2 expression and total cell numbers in the ganglionic eminence in the early developing human forebrain. Dev Neurosci 2010; 32:149–162.

    Article  CAS  PubMed  Google Scholar 

  58. Stoykova A, Treichel D, Hallonet M et al. Pax6 modulates the dorsoventral patterning of the mammalian telencephalon. J Neurosci 2000; 20:8042–8050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chapouton P, Gartner A, Gotz M. The role of Pax6 in restricting cell migration between developing cortex and basal ganglia. Development 1999; 126:5569–5579.

    CAS  PubMed  Google Scholar 

  60. Okladnova O, Syagailo YV, Mossner R et al. Regulation of PAX-6 gene transcription: alternate promoter usage in human brain. Brain Res Mol Brain Res 1998; 60:177–192.

    Article  CAS  PubMed  Google Scholar 

  61. Schedl A, Ross A, Lee M et al. Influence of pax6 gene dosage on development: overexpression causes severe eye abnormalities. Cell 1996; 86:71–82.

    Article  CAS  PubMed  Google Scholar 

  62. Han W, Leung KH, Fung WY et al. Association of pax6 polymorphisms with high myopia in han chinese nuclear families. Investigative Ophthalmology and Visual Science 2009; 50:47–56. doi: 10.1167/iovs.07-0813.

    Article  PubMed  Google Scholar 

  63. Jiang B, Yap MKH, Leung KH et al. pax6 haplotypes are associated with high myopia in han Chinese. PLoS ONE 2011; 6:el9587.doi:10.1371/journal.pone.0019587.

    Google Scholar 

  64. Lawson MJ, Zhang L. Housekeeping and tissue-specific genes differ in simple sequence repeats in the 5′-UTR region. Gene 2008; 407:54–62.

    Article  CAS  PubMed  Google Scholar 

  65. Warren WC, Hillier LW, Marshall Graves JA et al. Genome analysis of the platypus reveals unique signatures of evolution. Nature 2008; 453:175–183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jaworski A, Higgins NP, Wells RD et al. Topoisomerase mutants and physiological conditions control super coiling and Z-DNA formation in vivo. J Biol Chem 1991; 266:2576–2581.

    CAS  PubMed  Google Scholar 

  67. Wolfl S, Martinez C, Rich A et al. Transcription of the human corticotropin-releasing hormone gene in NPLC cells is correlated with Z-DNA formation. Proc Natl Acad Sci U S A 1996; 93:3664–3668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wittig B, Wolfl S, Dorbic T et al. Transcription of human c-myc in permeabilized nuclei is associated with formation of Z-DNA in three discrete regions of the gene. EMBO J 1992; 11:4653–4663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Li H, Xiao J, Li J et al. Human genomic Z-DNA segments probed by the Z alpha domain of ADAR1. Nucleic Acids Res 2009; 37:2737–2746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Schroth GP, Chou PJ, Ho PS. Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes. J Biol Chem 1992; 267:11846–11855.

    CAS  PubMed  Google Scholar 

  71. Wong B, Chen S, Kwon JA et al. Characterization of Z-DNA as a nucleosome-boundary element in yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 2007; 104:2229–2234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Liu H, Mulholland N, Fu H et al. Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling. Molecular Cell Biology 2006; 26:2550–2559.

    Article  CAS  Google Scholar 

  73. Zhang J, Ohta T, Maruyama A et al. BRG1 interacts with Nrf2 to selectively mediate HO-1 induction in response to oxidative stress. Mol Cell Biol 2006; 26:7942–7952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Xu YZ, Thuraisingam T, Marino R et al. Recruitment of SWI/SNF complex is required for transcriptional activation of SLC11A1 gene during macrophage differentiation of HL-60 cells. J Biol Chem 2011.

    Google Scholar 

  75. Peck LJ, Wang JC. Transcriptional block caused by a negative supercoiling induced structural change in an alternating CG sequence. Cell 1985; 40:129–137.

    Article  CAS  PubMed  Google Scholar 

  76. Wittig B, Dorbic T, Rich A. Transcription is associated with Z-DNA formation in metabolically active permeabilized mammalian cell nuclei. Proc Natl Acad Sci USA 1991; 88:2259–2263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Tae HJ, Luo X, Kim KH. Roles of CCAAT/enhancer-binding protein and its binding site on repression and derepression of acetyl-CoA carboxylase gene. J Biol Chem 1994; 269:10475–10484.

    CAS  PubMed  Google Scholar 

  78. Wu T, Ikezono T, Angus CW et al. Characterization of the promoter for the human 85 kDa cytosolic phospholipase A2 gene. Nucleic Acids Res 1994; 22:5093–5098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kulish VV, Heng L, Droge P. Z-dna-induced super-transport of energy within genomes. Physica A: Statistical Mechanics and its Applications 2007; 384:733 738. doi:DOI: 10.1016/j.physa.2007.06.023.

    Article  CAS  Google Scholar 

  80. Johnston BH. The S1-sensitive form of d(C-T)n.d(A-G)n: chemical evidence for a three-stranded structure in plasmids. Science 1988; 241:1800–1804.

    Article  CAS  PubMed  Google Scholar 

  81. Kohwi Y, Kohwi-Shigematsu T. Altered gene expression correlates with DNA structure. Genes Dev 1991; 5:2547–2554.

    Article  CAS  PubMed  Google Scholar 

  82. Maiti AK, Brahmachari SK. Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae. BMC Mol Biol 2001; 2:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Amiri H, Nekhotiaeva N, Sun JS et al. Benzoquinoquinoxaline derivatives stabilize and cleave H-DNA and repress transcription downstream of a triplex-forming sequence. J Mol Biol 2005; 351:776–783.

    Article  CAS  PubMed  Google Scholar 

  84. Motallebipour M, Rada-Iglesias A, Westin G et al. Two polypyrimidine tracts in the nitric oxide synthase 2 gene: similar regulatory sequences with different properties. Mol Biol Rep 2010; 37:2021–2030.

    Article  CAS  PubMed  Google Scholar 

  85. Lu Q, Wallrath LL, Granok H et al. (CT)n (GA)n repeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26 gene. Mol Cell Biol 1993; 13:2802–2814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Lu Q, Teare JM, Granok H et al. The capacity to form H-DNA cannot substitute for GAGA factor binding to a (CT)n*(GA)n regulatory site. Nucleic Acids Res 2003; 31:2483–2494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Matharu NK, Hussain T, Sankaranarayanan R et al. Vertebrate homologue of Drosophila GAGA factor. J Mol Biol 2010; 400:434–447.

    Article  CAS  PubMed  Google Scholar 

  88. Beaulieu M, Barbeau B, Rassart E. Triplex-forming oligonucleotides with unexpected affinity for a nontargeted GA repeat sequence. Antisense Nucleic Acid Drug Dev 1997; 7:125–130.

    Article  CAS  PubMed  Google Scholar 

  89. Rustighi A, Tessari MA, Vascotto F et al. A polypyrimidine/polypurine tract within the Hmga2 minimal promoter: a common feature of many growth-related genes. Biochemistry 2002; 41:1229–1240.

    Article  CAS  PubMed  Google Scholar 

  90. Han YJ, de Lanerolle P. Naturally extended CT. AG repeats increase H-DNA structures and promoter activity in the smooth muscle myosin light chain kinase gene. Mol Cell Biol 2008; 28:863–872.

    CAS  PubMed  Google Scholar 

  91. Nowling TK, Fulton JD, Chike-Harris K et al. Ets factors and a newly identified polymorphism regulate Flil promoter activity in lymphocytes. Mol Immunol 2008; 45:1–12.

    Article  CAS  PubMed  Google Scholar 

  92. Morris EE, Amria MY, Kistner-Grifn E et al. A GA microsatellite in the Flil promoter modulates gene expression and is associated with systemic lupus erythematosus patients without nephritis. Arthritis Res Ther 2010; 12:R212.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Zhang L, Eddy A, Teng YT et al. An immunological renal disease in transgenic mice that overexpress Fli-1, a member of the ets family of transcription factor genes. Mol Cell Biol 1995; 15:6961–6970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Borrmann L, Seebeck B, Rogalla P et al. Human hmga2 promoter is coregulated by a polymorphic dinucleotide (TC)-repeat. Oncogene 2003; 22:756–760.

    Article  CAS  PubMed  Google Scholar 

  95. Zhou X, Benson KF, Ashar HR et al. Mutation responsible for the mouse pygmy phenotype in the develop mentally regulated factor HMGI-C. Nature 1995; 376:771–774.

    Article  CAS  PubMed  Google Scholar 

  96. Hodge JC, T Cuenco K, Huyck KL et al. Uterine leiomyomata and decreased height: a common hmga2 predisposition allele. Hum Genet 2009; 125:257–263.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Lanktree MB, Guo Y, Murtaza M et al. Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height. Am J Hum Genet 2011; 88:6–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Suter B, Schnappauf G, Thoma F. Poly(dA.dT) sequences exist as rigid DNA structures in nucleosome-free yeast promoters in vivo. Nucleic Acids Res 2000; 28:4083–4089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Shimizu M, Mori T, Sakurai T et al. Destabilization of nucleosomes by an unusual DNA conformation adopted by poly(dA) small middle poly(dT) tracts in vivo. EMBO J 2000; 19:3358–3365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bao Y, White CL, Luger K. Nucleosome core particles containing apoly(dA.dT) sequence element exhibit a locally distorted DNA structure. J Mol Biol 2006; 361:617–624.

    Article  CAS  PubMed  Google Scholar 

  101. Segal E, Widom J. Poly(dA:dT) tracts: major determinants of nucleosome organization. Curr Opin Struct Biol 2009; 19:65–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Struhl K. Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. Proc Natl Acad Sci USA 1985; 82:8419–8423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wu R, Li H. Positioned and G/C-capped poly(dA:dT) tracts associate with the centers of nucleosome-free regions in yeast promoters. Genome Res 2010; 20:473–484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Uhlemann AC, Szlezak NA, Vonthein R et al. DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria. J Infect Dis 2004; 189:2227–2234.

    Article  CAS  PubMed  Google Scholar 

  105. Spek CA, Bertina RM, Reitsma PH. Unique distance and DNA-turn-dependent interactions in the human protein C gene promoter confer submaximal transcriptional activity. Biochem J 1999; 340:513–518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Vardhanabhuti S, Wang J, Hannenhalli S. Position and distance specificity are important determinants of cis-regulatory motifs in addition to evolutionary conservation. Nucleic Acids Res 2007; 35:3203–3213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88:323–331.

    Article  CAS  PubMed  Google Scholar 

  108. Ebihara M, Ohba H, Hattori E et al. Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility. Am J Med Genet B Neuropsychiatr. Genet 2003; 118B:32–35.

    Google Scholar 

  109. Loesch D, Hagerman R. Unstable mutations in the FMR1 gene and the phenotypes. In: Hannan AJ, ed. Tandem Repeat Polymorphisms: Genetic Plasticity, Neural Diversity and Disease. Austin/New York: Landes Bioscience/Springer Science+Business Media, 2012:78–114.

    Google Scholar 

  110. Darlow JM, Leach DR. Secondary structures in d(CGG) and d(CCG) repeattracts. JMolBiol 1998; 275:3–16.

    CAS  Google Scholar 

  111. Qin Y, Hurley LH. Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions. Biochimie 2008; 90:1149–1171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Shklover J, Weisman-Shomer P, Yafe A et al. Quadruplex structures of muscle gene promoter sequences enhance in vivo MyoD-dependent gene expression. Nucleic Acids Res 2010; 38:2369–2377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Matsugami A, Ouhashi K, Kanagawa M et al. An intramolecular quadruplex of (GGA)(4) triplet repeat DNA with a G:G:G:G tetrad and a G(:A):G(:A):G(:A):G heptad and its dimeric interaction. J Mol Biol 2001; 313:255–269.

    Article  CAS  PubMed  Google Scholar 

  114. Palumbo SL, Memmott RM, Uribe DJ et al. A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Res 2008; 36:1755–1769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Hafner M, Zimmermann K, Pottgiesser J et al. A purine-rich sequence in the human BM-40 gene promoter region is a prerequisite for maximum transcription. Matrix Biol 1995; 14:733–741.

    Article  CAS  PubMed  Google Scholar 

  116. Chamboredon S, Briggs J, Vial E et al. v-Jun downregulates the SPARC target gene by binding to the proximal promoter indirectly through Sp1/3. Oncogene 2003; 22:4047–4061.

    Article  CAS  PubMed  Google Scholar 

  117. Edwards S, Sirito M, Krahe R et al. A Z-DNA sequence reduces slipped-strand structure formation in the myotonic dystrophy type 2 (CCTG) x (CAGG) repeat. Proc Natl Acad Sci USA 2009; 106:3270–3275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kashi Y, King DG. Simple Sequence repeats as advantageous mutators in evolution. TRENDS in Genetics 2006; 22:253–259.

    Article  CAS  PubMed  Google Scholar 

  119. King DG. Evolution of simple sequence repeats as mutable sites. In: Hannan AJ, ed. Tandem Repeat Polymorphisms: Genetic Plasticity, Neural Diversity and Disease. Austin/New York: Landes Bioscience/ Springer Science+Business Media, 2012:10–25.

    Google Scholar 

  120. Buschiazzo E, Gemmell NJ. Conservation of human microsatellites across 450 million years of evolution. Genome Biol Evol 2010; 2:153–165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand

    Sterling M. Sawaya & Neil J. Gemmell

  2. Department of Pathology, University of Otago-Christchurch, Christchurch, New Zealand

    Andrew T. Bagshaw

  3. School of Natural Sciences, University of California-Merced, Merced, California, USA

    Emmanuel Buschiazzo

Authors
  1. Sterling M. Sawaya
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  2. Andrew T. Bagshaw
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  3. Emmanuel Buschiazzo
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  4. Neil J. Gemmell
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Corresponding author

Correspondence to Sterling M. Sawaya .

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Editors and Affiliations

  1. Florey Neuroscience Institutes, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia

    Anthony J. Hannan Phd

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© 2012 Landes Bioscience and Springer Science+Business Media

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Sawaya, S.M., Bagshaw, A.T., Buschiazzo, E., Gemmell, N.J. (2012). Promoter Microsatellites as Modulators of Human Gene Expression. In: Hannan, A.J. (eds) Tandem Repeat Polymorphisms. Advances in Experimental Medicine and Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5434-2_4

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