Pax6 Interactions with Chromatin and Identification of Its Novel Direct Target Genes in Lens and Forebrain

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  Xie, Qing ^a   Yang, Ying ^a   Huang, Jie ^b   Ninkovic, Jovica ^c,d   Walcher, Tessa ^c,d   Wolf, Louise ^a   Vitenzon, Ariel ^a   Zheng, Deyou ^a   Götz, Magdalena ^c,d   Beebe, David C ^b   Zavadil, Jiri ^e,f   Cvekl, Ales ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c INSTITUTE OF EPIDEMIOLOGY   (Germany)

^d UNIVERSITY OF MUNICH   (Germany)

^e NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^f INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR PAX6;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DNA MICROARRAY; EFNB2 GENE; EMBRYO; EMBRYO DEVELOPMENT; EYE DEVELOPMENT; FAT4 GENE; GAA GENE; GENE; GENE ACTIVATION; GENE CONTROL; GENE EXPRESSION REGULATION; GENE IDENTIFICATION; GENE INTERACTION; HAS2 GENE; IN SITU HYBRIDIZATION; IN VIVO STUDY; ISL1 GENE; KIF1B GENE; MOUSE; MTMR2 GENE; NAV1 GENE; NEWBORN; NONHUMAN; NUCLEOTIDE SEQUENCE; PAX6 GENE; PCSK1N GENE; PROMOTER REGION; SNCA GENE; TISSUE SPECIFICITY; TRPM3 GENE;

ANIMALS; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; COMPUTATIONAL BIOLOGY; EYE PROTEINS; HOMEODOMAIN PROTEINS; LENS, CRYSTALLINE; MICE; PAIRED BOX TRANSCRIPTION FACTORS; PROSENCEPHALON; PROTEIN BINDING; REPRESSOR PROTEINS;

EID: 84872308179     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0054507     Document Type: Article

References (125)

1. Barolo S, Posakony JW, (2002) Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 16: 1167-1181.
2. Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM, (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10: 252-263.
3. Cvekl A, Mitton KP, (2010) Epigenetic regulatory mechanisms in vertebrate eye development and disease. Heredity (Edinb) 105: 135-151.
4. Davidson EH, (2010) Emerging properties of animal gene regulatory networks. Nature 468: 911-920.
5. Peter IS, Davidson EH, (2011) Evolution of gene regulatory networks controlling body plan development. Cell 144: 970-985.
6. Biggin MD, (2011) Animal transcription networks as highly connected, quantitative continua. Dev Cell 21: 611-626.
7. Cvekl A, Piatigorsky J, (1996) Lens development and crystallin gene expression: many roles for Pax-6. Bioessays 18: 621-630.
8. Cvekl A, Yang Y, Chauhan BK, Cveklova K, (2004) Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens. Int J Dev Biol 48: 829-844.
9. Dohrmann C, Gruss P, Lemaire L, (2000) Pax genes and the differentiation of hormone-producing endocrine cells in the pancreas. Mech Dev 92: 47-54.
10. Gotz M, Huttner WB, (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6: 777-788.
11. Nomura T, Haba H, Osumi N, (2007) Role of a transcription factor Pax6 in the developing vertebrate olfactory system. Dev Growth Differ 49: 683-690.
12. Osumi N, Shinohara H, Numayama-Tsuruta K, Maekawa M, (2008) Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells 26: 1663-1672.
13. Simpson TI, Price DJ, (2002) Pax6; a pleiotropic player in development. Bioessays 24: 1041-1051.
14. Callaerts P, Halder G, Gehring WJ, (1997) PAX-6 in development and evolution. Annu Rev Neurosci 20: 483-532.
15. Erclik T, Hartenstein V, McInnes RR, Lipshitz HD, (2009) Eye evolution at high resolution: the neuron as a unit of homology. Dev Biol 332: 70-79.
16. Jonasova K, Kozmik Z, (2008) Eye evolution: lens and cornea as an upgrade of animal visual system. Semin Cell Dev Biol 19: 71-81.
17. Suga H, Tschopp P, Graziussi DF, Stierwald M, Schmid V, et al. (2010) Flexibly deployed Pax genes in eye development at the early evolution of animals demonstrated by studies on a hydrozoan jellyfish. Proc Natl Acad Sci U S A 107: 14263-14268.
18. Graw J, (2010) Eye development. Curr Top Dev Biol 90: 343-386.
19. van Heyningen V, Williamson KA, (2002) PAX6 in sensory development. Hum Mol Genet 11: 1161-1167.
20. Ashery-Padan R, Marquardt T, Zhou X, Gruss P, (2000) Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev 14: 2701-2711.
21. Grindley JC, Davidson DR, Hill RE, (1995) The role of Pax-6 in eye and nasal development. Development 121: 1433-1442.
22. Baulmann DC, Ohlmann A, Flugel-Koch C, Goswami S, Cvekl A, et al. (2002) Pax6 heterozygous eyes show defects in chamber angle differentiation that are associated with a wide spectrum of other anterior eye segment abnormalities. Mech Dev 118: 3-17.
23. Collinson JM, Quinn JC, Buchanan MA, Kaufman MH, Wedden SE, et al. (2001) Primary defects in the lens underlie complex anterior segment abnormalities of the Pax6 heterozygous eye. Proc Natl Acad Sci U S A 98: 9688-9693.
24. van Raamsdonk CD, Tilghman SM, (2000) Dosage requirement and allelic expression of PAX6 during lens placode formation. Development 127: 5439-5448.
25. Shaham O, Smith AN, Robinson ML, Taketo MM, Lang RA, et al. (2009) Pax6 is essential for lens fiber cell differentiation. Development 136: 2567-2578.
26. Wolf LV, Yang Y, Wang J, Xie Q, Braunger B, et al. (2009) Identification of pax6-dependent gene regulatory networks in the mouse lens. PLoS One 4: e4159.
27. Chauhan BK, Yang Y, Cveklova K, Cvekl A, (2004) Functional interactions between alternatively spliced forms of Pax6 in crystallin gene regulation and in haploinsufficiency. Nucleic Acids Res 32: 1696-1709.
28. Yang Y, Chauhan BK, Cveklova K, Cvekl A, (2004) Transcriptional regulation of mouse alphaB- and gammaF-crystallin genes in lens: opposite promoter-specific interactions between Pax6 and large Maf transcription factors. J Mol Biol 344: 351-368.
29. Yang Y, Cvekl A, (2005) Tissue-specific regulation of the mouse alphaA-crystallin gene in lens via recruitment of Pax6 and c-Maf to its promoter. J Mol Biol 351: 453-469.
30. Hack MA, Saghatelyan A, de Chevigny A, Pfeifer A, Ashery-Padan R, et al. (2005) Neuronal fate determinants of adult olfactory bulb neurogenesis. Nat Neurosci 8: 865-872.
31. Kohwi M, Osumi N, Rubenstein JL, Alvarez-Buylla A, (2005) Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. J Neurosci 25: 6997-7003.
32. Ninkovic J, Pinto L, Petricca S, Lepier A, Sun J, et al. (2010) The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin alphaA. Neuron 68: 682-694.
33. St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P, (1997) Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature 387: 406-409.
34. Sander M, Neubuser A, Kalamaras J, Ee HC, Martin GR, et al. (1997) Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 11: 1662-1673.
35. Laakso M, (2009) Not for the eyes only: PAX6 and glucose metabolism. Diabetologia 52: 381-384.
36. Gosmain Y, Marthinet E, Cheyssac C, Guerardel A, Mamin A, et al. (2010) Pax6 controls the expression of critical genes involved in pancreatic {alpha} cell differentiation and function. J Biol Chem 285: 33381-33393.
37. Dames P, Puff R, Weise M, Parhofer KG, Goke B, et al. (2010) Relative roles of the different Pax6 domains for pancreatic alpha cell development. BMC Dev Biol 10: 39.
38. Ashery-Padan R, Zhou X, Marquardt T, Herrera P, Toube L, et al. (2004) Conditional inactivation of Pax6 in the pancreas causes early onset of diabetes. Dev Biol 269: 479-488.
39. Yang Y, Stopka T, Golestaneh N, Wang Y, Wu K, et al. (2006) Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. EMBO J 25: 2107-2118.
40. Ostrin EJ, Li Y, Hoffman K, Liu J, Wang K, et al. (2006) Genome-wide identification of direct targets of the Drosophila retinal determination protein Eyeless. Genome Res 16: 466-476.
41. Michaut L, Flister S, Neeb M, White KP, Certa U, et al. (2003) Analysis of the eye developmental pathway in Drosophila using DNA microarrays. Proc Natl Acad Sci U S A 100: 4024-4029.
42. Nfonsam LE, Cano C, Mudge J, Schilkey FD, Curtiss J, (2012) Analysis of the Transcriptomes Downstream of Eyeless and the Hedgehog, Decapentaplegic and Notch Signaling Pathways in Drosophila melanogaster. PLoS One 7: e44583.
43. Coutinho P, Pavlou S, Bhatia S, Chalmers KJ, Kleinjan DA, et al. (2011) Discovery and assessment of conserved Pax6 target genes and enhancers. Genome Res 21: 1349-1359.
44. Sansom SN, Griffiths DS, Faedo A, Kleinjan DJ, Ruan Y, et al. (2009) The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis. PLoS Genet 5: e1000511.
45. Holm PC, Mader MT, Haubst N, Wizenmann A, Sigvardsson M, et al. (2007) Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon. Mol Cell Neurosci 34: 99-119.
46. Johnson WE, Li W, Meyer CA, Gottardo R, Carroll JS, et al. (2006) Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A 103: 12457-12462.
47. Oron-Karni V, Farhy C, Elgart M, Marquardt T, Remizova L, et al. (2008) Dual requirement for Pax6 in retinal progenitor cells. Development 135: 4037-4047.
48. Xie Q, Cvekl A, (2011) The orchestration of mammalian tissue morphogenesis through a series of coherent feed-forward loops. J Biol Chem 286: 43259-43271.
49. Wilson DS, Guenther B, Desplan C, Kuriyan J, (1995) High resolution crystal structure of a paired (Pax) class cooperative homeodomain dimer on DNA. Cell 82: 709-719.
50. Xu HE, Rould MA, Xu W, Epstein JA, Maas RL, et al. (1999) Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding. Genes Dev 13: 1263-1275.
51. Grant CE, Bailey TL, Noble WS, (2011) FIMO: scanning for occurrences of a given motif. Bioinformatics 27: 1017-1018.
52. Hill RE, Favor J, Hogan BL, Ton CC, Saunders GF, et al. (1991) Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354: 522-525.
53. Aota S, Nakajima N, Sakamoto R, Watanabe S, Ibaraki N, et al. (2003) Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene. Dev Biol 257: 1-13.
54. Machon O, Kreslova J, Ruzickova J, Vacik T, Klimova L, et al. (2010) Lens morphogenesis is dependent on Pax6-mediated inhibition of the canonical Wnt/beta-catenin signaling in the lens surface ectoderm. Genesis 48: 86-95.
55. Bibel M, Richter J, Schrenk K, Tucker KL, Staiger V, et al. (2004) Differentiation of mouse embryonic stem cells into a defined neuronal lineage. Nat Neurosci 7: 1003-1009.
56. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, et al. (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27: 275-280.
57. LaVaute TM, Yoo YD, Pankratz MT, Weick JP, Gerstner JR, et al. (2009) Regulation of neural specification from human embryonic stem cells by BMP and FGF. Stem Cells 27: 1741-1749.
58. Zhang X, Huang CT, Chen J, Pankratz MT, Xi J, et al. (2010) Pax6 is a human neuroectoderm cell fate determinant. Cell Stem Cell 7: 90-100.
59. Shankaranarayanan P, Mendoza-Parra MA, Walia M, Wang L, Li N, et al. (2011) Single-tube linear DNA amplification (LinDA) for robust ChIP-seq. Nat Methods 8: 565-567.
60. Delacroix L, Moutier E, Altobelli G, Legras S, Poch O, et al. (2010) Cell-specific interaction of retinoic acid receptors with target genes in mouse embryonic fibroblasts and embryonic stem cells. Mol Cell Biol 30: 231-244.
61. Cao Y, Kumar RM, Penn BH, Berkes CA, Kooperberg C, et al. (2006) Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters. EMBO J 25: 502-511.
62. John S, Sabo PJ, Thurman RE, Sung MH, Biddie SC, et al. (2011) Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat Genet 43: 264-268.
63. Gordan R, Hartemink AJ, Bulyk ML, (2009) Distinguishing direct versus indirect transcription factor-DNA interactions. Genome Res 19: 2090-2100.
64. Soleimani VD, Punch VG, Kawabe Y, Jones AE, Palidwor GA, et al. (2012) Transcriptional dominance of Pax7 in adult myogenesis is due to high-affinity recognition of homeodomain motifs. Dev Cell 22: 1208-1220.
65. He S, Pirity MK, Wang WL, Wolf L, Chauhan BK, et al. (2010) Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and its denucleation. Epigenetics Chromatin 3: 21.
66. Liu T, Zhao Y, Tang N, Feng R, Yang X, et al. (2012) Pax6 Directly Down-Regulates Pcsk1n Expression Thereby Regulating PC1/3 Dependent Proinsulin Processing. PLoS One 7: e46934.
67. Nangaku M, Sato-Yoshitake R, Okada Y, Noda Y, Takemura R, et al. (1994) KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79: 1209-1220.
68. Lyons DA, Naylor SG, Scholze A, Talbot WS, (2009) Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons. Nat Genet 41: 854-858.
69. Chandra S, Fornai F, Kwon HB, Yazdani U, Atasoy D, et al. (2004) Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc Natl Acad Sci U S A 101: 14966-14971.
70. Tong Y, Shen J, (2009) alpha-synuclein and LRRK2: partners in crime. Neuron 64: 771-773.
71. Winslow AR, Chen CW, Corrochano S, Acevedo-Arozena A, Gordon DE, et al. (2010) alpha-Synuclein impairs macroautophagy: implications for Parkinson's disease. J Cell Biol 190: 1023-1037.
72. Kokhan VS, Afanasyeva MA, Van'kin GI, (2012) alpha-Synuclein knockout mice have cognitive impairments. Behav Brain Res.
73. DeRuisseau LR, Fuller DD, Qiu K, DeRuisseau KC, Donnelly WH Jr, et al. (2009) Neural deficits contribute to respiratory insufficiency in Pompe disease. Proc Natl Acad Sci U S A 106: 9419-9424.
74. Pokorny KS, Ritch R, Friedman AH, Desnick RJ, (1982) Ultrastructure of the eye in fetal type II glycogenosis (Pompe's disease). Invest Ophthalmol Vis Sci 22: 25-31.
75. Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, et al. (2001) Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105: 587-597.
76. Aulchenko YS, Hoppenbrouwers IA, Ramagopalan SV, Broer L, Jafari N, et al. (2008) Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat Genet 40: 1402-1403.
77. Davis LK, Meyer KJ, Rudd DS, Librant AL, Epping EA, et al. (2008) Pax6 3′ deletion results in aniridia, autism and mental retardation. Hum Genet 123: 371-378.
78. Maekawa M, Iwayama Y, Nakamura K, Sato M, Toyota T, et al. (2009) A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient. Neurosci Lett 462: 267-271.
79. Shinawi M, Sahoo T, Maranda B, Skinner SA, Skinner C, et al. (2011) 11p14.1 microdeletions associated with ADHD, autism, developmental delay, and obesity. Am J Med Genet A 155A: 1272-1280.
80. Thompson PJ, Mitchell TN, Free SL, Williamson KA, Hanson IM, et al. (2004) Cognitive functioning in humans with mutations of the PAX6 gene. Neurology 62: 1216-1218.
81. Sander T, Syagailo Y, Samochowiec J, Okladnova O, Lesch KP, et al. (1999) Association analysis of a regulatory promoter polymorphism of the PAX-6 gene with idiopathic generalized epilepsy. Epilepsy Res 36: 61-67.
82. Leonard M, Chan Y, Menko AS, (2008) Identification of a novel intermediate filament-linked N-cadherin/gamma-catenin complex involved in the establishment of the cytoarchitecture of differentiated lens fiber cells. Dev Biol 319: 298-308.
83. Straub BK, Boda J, Kuhn C, Schnoelzer M, Korf U, et al. (2003) A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells. J Cell Sci 116: 4985-4995.
84. Kuracha MR, Burgess D, Siefker E, Cooper JT, Licht JD, et al. (2011) Spry1 and Spry2 are necessary for lens vesicle separation and corneal differentiation. Invest Ophthalmol Vis Sci 52: 6887-6897.
85. Smith AN, Radice G, Lang RA, (2010) Which FGF ligands are involved in lens induction? Dev Biol 337: 195-198.
86. Molotkov A, Molotkova N, Duester G, (2006) Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning. Development 133: 1901-1910.
87. Cheng C, Gong X, (2011) Diverse roles of Eph/ephrin signaling in the mouse lens. PLoS One 6: e28147.
88. Senturk A, Pfennig S, Weiss A, Burk K, Acker-Palmer A, (2011) Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration. Nature 472: 356-360.
89. Saburi S, Hester I, Fischer E, Pontoglio M, Eremina V, et al. (2008) Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat Genet 40: 1010-1015.
90. Sugiyama Y, Lovicu FJ, McAvoy JW, (2011) Planar cell polarity in the mammalian eye lens. Organogenesis 7: 191-201.
91. Zhang N, Bai H, David KK, Dong J, Zheng Y, et al. (2010) The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell 19: 27-38.
92. Stern R, Asari AA, Sugahara KN, (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85: 699-715.
93. Rodgers LS, Lalani S, Hardy KM, Xiang X, Broka D, et al. (2006) Depolymerized hyaluronan induces vascular endothelial growth factor, a negative regulator of developmental epithelial-to-mesenchymal transformation. Circ Res 99: 583-589.
94. Tien JY, Spicer AP, (2005) Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns. Dev Dyn 233: 130-141.
95. Chauhan BK, Lou M, Zheng Y, Lang RA, (2011) Balanced Rac1 and RhoA activities regulate cell shape and drive invagination morphogenesis in epithelia. Proc Natl Acad Sci U S A 108: 18289-18294.
96. Huang J, Rajagopal R, Liu Y, Dattilo LK, Shaham O, et al. (2011) The mechanism of lens placode formation: a case of matrix-mediated morphogenesis. Dev Biol 355: 32-42.
97. Urness LD, Paxton CN, Wang X, Schoenwolf GC, Mansour SL, (2010) FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol 340: 595-604.
98. Martinez-Lopez MJ, Alcantara S, Mascaro C, Perez-Branguli F, Ruiz-Lozano P, et al. (2005) Mouse neuron navigator 1, a novel microtubule-associated protein involved in neuronal migration. Mol Cell Neurosci 28: 599-612.
99. Feng J, Zhou Y, Campbell SL, Le T, Li E, et al. (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13: 423-430.
100. Duparc RH, Boutemmine D, Champagne MP, Tetreault N, Bernier G, (2006) Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice. Dev Biol 300: 647-655.
101. Nasonkin IO, Lazo K, Hambright D, Brooks M, Fariss R, et al. (2011) Distinct nuclear localization patterns of DNA methyltransferases in developing and mature mammalian retina. J Comp Neurol 519: 1914-1930.
102. Niehrs C, (2006) Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 25: 7469-7481.
103. Kiselev Y, Eriksen TE, Forsdahl S, Nguyen LH, Mikkola I, (2012) 3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a)- A New Tool Used for Identification of Common and Isoform Specific Target Genes. PLoS One 7: e31915.
104. Numayama-Tsuruta K, Arai Y, Takahashi M, Sasaki-Hoshino M, Funatsu N, et al. (2010) Downstream genes of Pax6 revealed by comprehensive transcriptome profiling in the developing rat hindbrain. BMC Dev Biol 10: 6.
105. Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, et al. (2002) Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci 5: 308-315.
106. Marquardt T, Gruss P, (2002) Generating neuronal diversity in the retina: one for nearly all. Trends Neurosci 25: 32-38.
107. Secker GA, Daniels JT, (2008) Corneal epithelial stem cells: deficiency and regulation. Stem Cell Rev 4: 159-168.
108. Madhavan M, Haynes TL, Frisch NC, Call MK, Minich CM, et al. (2006) The role of Pax-6 in lens regeneration. Proc Natl Acad Sci U S A 103: 14848-14853.
109. Efrat S, Surana M, Fleischer N, (1991) Glucose induces insulin gene transcription in a murine pancreatic beta-cell line. J Biol Chem 266: 11141-11143.
110. Ji X, Li W, Song J, Wei L, Liu XS, (2006) CEAS: cis-regulatory element annotation system. Nucleic Acids Res 34: W551-554.
111. Huang da W, Sherman BT, Lempicki RA, (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1-13.
112. Czerny T, Busslinger M, (1995) DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5). Mol Cell Biol 15: 2858-2871.
113. Thaung C, West K, Clark BJ, McKie L, Morgan JE, et al. (2002) Novel ENU-induced eye mutations in the mouse: models for human eye disease. Hum Mol Genet 11: 755-767.
114. Yamaguchi Y, Sawada J, Yamada M, Handa H, Azuma N, (1997) Autoregulation of Pax6 transcriptional activation by two distinct DNA-binding subdomains of the paired domain. Genes Cells 2: 255-261.
115. Davis A, Cowell JK, (1993) Mutations in the PAX6 gene in patients with hereditary aniridia. Hum Mol Genet 2: 2093-2097.
116. D'Elia AV, Puppin C, Pellizzari L, Pianta A, Bregant E, et al. (2006) Molecular analysis of a human PAX6 homeobox mutant. Eur J Hum Genet 14: 744-751.
117. Chauhan BK, Yang Y, Cveklova K, Cvekl A, (2004) Functional properties of natural human PAX6 and PAX6(5a) mutants. Invest Ophthalmol Vis Sci 45: 385-392.
118. Cvekl A, Kashanchi F, Sax CM, Brady JN, Piatigorsky J, (1995) Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site. Mol Cell Biol 15: 653-660.
119. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3: RESEARCH0034.
120. Pinto LW, Araujo MB, Vettore AL, Wernersbach L, Leite AC, et al. (2008) Glioblastomas: correlation between oligodendroglial components, genetic abnormalities, and prognosis. Virchows Arch 452: 481-490.
121. Bijvoet AG, van de Kamp EH, Kroos MA, Ding JH, Yang BZ, et al. (1998) Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease. Hum Mol Genet 7: 53-62.
122. Bolino A, Bolis A, Previtali SC, Dina G, Bussini S, et al. (2004) Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis. J Cell Biol 167: 711-721.
123. Fricker LD, McKinzie AA, Sun J, Curran E, Qian Y, et al. (2000) Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J Neurosci 20: 639-648.
124. Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, et al. (2001) beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc Natl Acad Sci U S A 98: 12245-12250.
125. Pan L, Deng M, Xie X, Gan L, (2008) ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells. Development 135: 1981-1990.