Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (61)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Kleinjan, D. A.
Right arrow Articles by van Heyningen, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kleinjan, D. A.
Right arrow Articles by van Heyningen, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2001, Vol. 10, No. 19 2049-2059
© 2001 Oxford University Press

Aniridia-associated translocations, DNase hypersensitivity, sequence comparison and transgenic analysis redefine the functional domain of PAX6

Dirk A. Kleinjan, Anne Seawright, Andreas Schedl, Roy A Quinlan1, Sarah Danes and Veronica van Heyningen+

MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK and 1Department of Biochemistry, Medical Sciences Institute/Wellcome Trust Building Complex, University of Dundee, Dundee DD1 5EH, UK

The transcription factor PAX6 plays a critical, evolutionarily conserved role in eye, brain and olfactory development. Homozygous loss of PAX6 function affects all expressing tissues and is neonatally lethal; heterozygous null mutations cause aniridia in humans and the Small eye (Sey) phenotype in mice. Several upstream and intragenic PAX6 control elements have been defined, generally through transgenesis. However, aniridia cases with chromosomal rearrangements far downstream of an intact PAX6 gene suggested a requirement for additional cis-acting control for correct gene expression. The likely location of such elements is pinpointed through YAC transgenic studies. A 420 kb yeast artificial chromosome (YAC) clone, extending well beyond the most distant patient breakpoint, was previously shown to rescue homozygous Small eye lethality and correct the heterozygous eye phenotype. We now show that a 310 kb YAC clone, terminating just 5' of the breakpoint, fails to influence the Sey phenotypes. Using evolutionary sequence comparison, DNaseI hypersensitivity analysis and transgenic reporter studies, we have identified a region, >150 kb distal to the major PAX6 promoter P1, containing regulatory elements. Components of this downstream regulatory region drive reporter expression in distinct partial PAX6 patterns, indicating that the functional PAX6 gene domain extends far beyond the transcription unit.

+ To whom correspondence should be addressed. Tel: +44 131 3322471; Fax: +44 131 3322620; Email: v.vanheyningen@hgu.mrc.ac.uk Present address: Andreas Schedl, Max Delbruck Centrum fur Molekulare Medizin, Robert Rossle Strasse 10, 13122 Berlin Buch, Germany


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 GeneticsHome page
J. Favor, A. Bradley, N. Conte, D. Janik, W. Pretsch, P. Reitmeir, M. Rosemann, W. Schmahl, J. Wienberg, and I. Zaus
Analysis of Pax6 Contiguous Gene Deletions in the Mouse, Mus musculus, Identifies Regions Distinct from Pax6 Responsible for Extreme Small-Eye and Belly-Spotting Phenotypes
Genetics, August 1, 2009; 182(4): 1077 - 1088.
[Abstract] [Full Text] [PDF]

Home page
 Brief Funct Genomic ProteomicHome page
D.-J. Kleinjan and P. Coutinho
Cis-ruption mechanisms: disruption of cis-regulatory control as a cause of human genetic disease
Brief Funct Genomic Proteomic, July 13, 2009; (2009) elp022v1.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Diamandis, A. D. Paterson, J. M. Rommens, D. K. Veljkovic, J. Blavignac, D. E. Bulman, J. S. Waye, F. Derome, G. E. Rivard, and C. P. M. Hayward
Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes
Blood, February 12, 2009; 113(7): 1543 - 1546.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
Y. Chen, Y.-q. Doughman, S. Gu, A. Jarrell, S.-i. Aota, A. Cvekl, M. Watanabe, S. L. Dunwoodie, R. S. Johnson, V. van Heyningen, et al.
Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis
Development, September 1, 2008; 135(17): 2939 - 2948.
[Abstract] [Full Text] [PDF]

Home page
 J Natl Cancer Inst MonogrHome page
C. Elso, X. Lu, S. Morrison, A. Tarver, H. Thompson, H. Thurkow, N. A. Yamada, and L. Stubbs
Germline Translocations in Mice: Unique Tools for Analyzing Gene Function and Long-Distance Regulatory Mechanisms
J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 91 - 95.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
J. Dong, E. Jimi, H. Zhong, M. S. Hayden, and S. Ghosh
Repression of gene expression by unphosphorylated NF-{kappa}B p65 through epigenetic mechanisms
Genes & Dev., May 1, 2008; 22(9): 1159 - 1173.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
F. M.D. Tholozan, C. Gribbon, Z. Li, M. W. Goldberg, A. R. Prescott, N. McKie, and R. A. Quinlan
FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability
Mol. Biol. Cell, November 1, 2007; 18(11): 4222 - 4231.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. A. Bien-Willner, P. Stankiewicz, and J. R. Lupski
SOX9cre1, a cis-acting regulatory element located 1.1 Mb upstream of SOX9, mediates its enhancement through the SHH pathway
Hum. Mol. Genet., May 15, 2007; 16(10): 1143 - 1156.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
N. Song, K. R. Schwab, L. T. Patterson, T. Yamaguchi, X. Lin, S. S. Potter, and R. A. Lang
pygopus 2 has a crucial, Wnt pathway-independent function in lens induction
Development, May 15, 2007; 134(10): 1873 - 1885.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
H. Kikuta, M. Laplante, P. Navratilova, A. Z. Komisarczuk, P. G. Engstrom, D. Fredman, A. Akalin, M. Caccamo, I. Sealy, K. Howe, et al.
Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates
Genome Res., May 1, 2007; 17(5): 545 - 555.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
N. Sabherwal, F. Bangs, R. Roth, B. Weiss, K. Jantz, E. Tiecke, G. K. Hinkel, C. Spaich, B. P. Hauffa, H. van der Kamp, et al.
Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients
Hum. Mol. Genet., January 15, 2007; 16(2): 210 - 222.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Liu and U. Francke
Identification of cis-regulatory elements for MECP2 expression
Hum. Mol. Genet., June 1, 2006; 15(11): 1769 - 1782.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
N. Davis-Silberman, T. Kalich, V. Oron-Karni, T. Marquardt, M. Kroeber, E. R. Tamm, and R. Ashery-Padan
Genetic dissection of Pax6 dosage requirements in the developing mouse eye
Hum. Mol. Genet., August 1, 2005; 14(15): 2265 - 2276.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. Noguchi, Y. Yokouchi, J. Zhang, K. Shibuya, A. Shibuya, M. Bannai, K. Tokunaga, H. Doi, M. Tamari, M. Shimizu, et al.
Positional Identification of an Asthma Susceptibility Gene on Human Chromosome 5q33
Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 183 - 188.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
G. G. Loots, M. Kneissel, H. Keller, M. Baptist, J. Chang, N. M. Collette, D. Ovcharenko, I. Plajzer-Frick, and E. M. Rubin
Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease
Genome Res., July 1, 2005; 15(7): 928 - 935.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. van Heyningen and P. L. Yeyati
Mechanisms of non-Mendelian inheritance in genetic disease
Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R225 - R233.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. B. Rankin, W. Xu, D. G. Silberg, and E. Suh
Putative intestine-specific enhancers located in 5' sequence of the CDX1 gene regulate CDX1 expression in the intestine
Am J Physiol Gastrointest Liver Physiol, May 1, 2004; 286(5): G872 - G880.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. R. FitzPatrick, I. M. Carr, L. McLaren, J. P. Leek, P. Wightman, K. Williamson, P. Gautier, N. McGill, C. Hayward, H. Firth, et al.
Identification of SATB2 as the cleft palate gene on 2q32-q33
Hum. Mol. Genet., October 1, 2003; 12(19): 2491 - 2501.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
D. P. Mortlock, C. Guenther, and D. M. Kingsley
A General Approach for Identifying Distant Regulatory Elements Applied to the Gdf6 Gene
Genome Res., September 1, 2003; 13(9): 2069 - 2081.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
D. A. Tyas, H. Pearson, P. Rashbass, and D. J. Price
Pax6 Regulates Cell Adhesion during Cortical Development
Cereb Cortex, June 1, 2003; 13(6): 612 - 619.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
X. Zhang, A. Friedman, S. Heaney, P. Purcell, and R. L. Maas
Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis
Genes & Dev., August 15, 2002; 16(16): 2097 - 2107.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. van Heyningen and K. A. Williamson
PAX6 in sensory development
Hum. Mol. Genet., May 15, 2002; 11(10): 1161 - 1167.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J.-K. Guo, A. L. Menke, M.-C. Gubler, A. R. Clarke, D. Harrison, A. Hammes, N. D. Hastie, and A. Schedl
WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis
Hum. Mol. Genet., March 1, 2002; 11(6): 651 - 659.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
N. Baumer, T. Marquardt, A. Stoykova, R. Ashery-Padan, K. Chowdhury, and P. Gruss
Pax6 is required for establishing naso-temporal and dorsal characteristics of the optic vesicle
Development, January 10, 2002; 129(19): 4535 - 4545.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. V. Jamieson, R. Perveen, B. Kerr, M. Carette, J. Yardley, E. Heon, M. G. Wirth, V. van Heyningen, D. Donnai, F. Munier, et al.
Domain disruption and mutation of the bZIP transcription factor, MAF,associated with cataract, ocular anterior segment dysgenesis and coloboma
Hum. Mol. Genet., January 1, 2002; 11(1): 33 - 42.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.