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Science 10 July 1992:
Vol. 257. no. 5067, pp. 235 - 237
DOI: 10.1126/science.1321494
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Articles

Science, Vol 257, Issue 5067, 235-237
Copyright © 1992 by American Association for the Advancement of Science

articles

Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript

WA Bickmore, K Oghene, MH Little, A Seawright, V van Heyningen, and ND Hastie

Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, Scotland.

The technique of whole-genome polymerase chain reaction was used to study the DNA binding properties of the product of the wt1 gene. The zinc finger region of this gene is alternatively spliced such that the major transcript encodes a protein with three extra amino acids between the third and fourth fingers. The minor form of the protein binds specifically to DNA. It is now shown that the major form of wt1 messenger RNA encodes a protein that binds to DNA with a specificity that differs from that of the minor form. Therefore, alternative splicing within the DNA binding domain of a transcription factor can generate proteins with distinct DNA binding specificities and probably different physiological targets.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Transcription Factor Wilms Tumor 1 Regulates Matrix Metalloproteinase-9 through a Nitric Oxide-Mediated Pathway.
M. Marcet-Palacios, M. Ulanova, F. Duta, L. Puttagunta, S. Munoz, D. Gibbings, M. Radomski, L. Cameron, I. Mayers, and A. D. Befus (2007)
J. Immunol. 179, 256-265
   Abstract »    Full Text »    PDF »
The Wilms' tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron.
Y. Bor, J. Swartz, A. Morrison, D. Rekosh, M. Ladomery, and M.-L. Hammarskjold (2006)
Genes & Dev. 20, 1597-1608
   Abstract »    Full Text »    PDF »
Identification of a DNA-binding site and transcriptional target for the EWS-WT1(+KTS) oncoprotein.
P. A. Reynolds, G. A. Smolen, R. E. Palmer, D. Sgroi, V. Yajnik, W. L. Gerald, and D. A. Haber (2003)
Genes & Dev. 17, 2094-2107
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An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli.
Y. Hashimoto, C. Zhang, J. Kawauchi, I. Imoto, M. T. Adachi, J. Inazawa, T. Amagasa, T. Hai, and S. Kitajima (2002)
Nucleic Acids Res. 30, 2398-2406
   Abstract »    Full Text »    PDF »
Cyclin E Is a Target of WT1 Transcriptional Repression.
D. M. Loeb, D. Korz, M. Katsnelson, E. A. Burwell, A. D. Friedman, and S. Sukumar (2002)
J. Biol. Chem. 277, 19627-19632
   Abstract »    Full Text »    PDF »
Loss of Imprinting of Insulin-Like Growth Factor-II (IGF2) Gene in Distinguishing Specific Biologic Subtypes of Wilms Tumor.
J. D. Ravenel, K. W. Broman, E. J. Perlman, E. L. Niemitz, T. M. Jayawardena, D. W. Bell, D. A. Haber, H. Uejima, and A. P. Feinberg (2001)
J Natl Cancer Inst 93, 1698-1703
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Insulin-Like Growth Factor-I Receptor Gene Expression in Prostate Cancer Cells.
S. E. Damon, S. R. Plymate, J. M. Carroll, C. C. Sprenger, C. Dechsukhum, J. L. Ware, and C. T. Roberts Jr. (2001)
Endocrinology 142, 21-27
   Abstract »    Full Text »    PDF »
Wilms' Tumor Suppressor Gene WT1: From Structure to Renal Pathophysiologic Features.
C. MROWKA and A. SCHEDL (2000)
J. Am. Soc. Nephrol. 11, 106S-115
   Abstract »    Full Text »
Molecular basis for modulation of biological function by alternate splicing of the Wilms' tumor suppressor protein.
J. H. Laity, H. J. Dyson, and P. E. Wright (2000)
PNAS 97, 11932-11935
   Abstract »    Full Text »    PDF »
Identification of WTAP, a novel Wilms' tumour 1-associating protein.
N. A. Little, N. D. Hastie, and R. C. Davies (2000)
Hum. Mol. Genet. 9, 2231-2239
   Abstract »    Full Text »    PDF »
Constitutional WT1 mutations correlate with clinical features in children with progressive nephropathy.
A. TAKATA, H. KIKUCHI, R. FUKUZAWA, S. ITO, M. HONDA, and J.-I. HATA (2000)
J. Med. Genet. 37, 698-701
   Full Text »
Did nucleotides or amino acids drive evolutionary conservation of the WT1 {+/-}KTS alternative splice?.
R. C. Davies, E. Bratt, and N. D. Hastie (2000)
Hum. Mol. Genet. 9, 1177-1183
   Abstract »    Full Text »    PDF »
Regulation of Insulin-Like Growth Factor I Receptor Promoter Activity by Wild-Type and Mutant Versions of the WT1 Tumor Suppressor.
K. Tajinda, J. Carroll, and C. T. Roberts Jr. (1999)
Endocrinology 140, 4713-4724
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Involvement of the Amino Terminus of the B2 Receptor in Agonist-induced Receptor Dimerization.
S. AbdAlla, E. Zaki, H. Lother, and U. Quitterer (1999)
J. Biol. Chem. 274, 26079-26084
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Dominant Negative Murine Serum Response Factor: Alternative Splicing within the Activation Domain Inhibits Transactivation of Serum Response Factor Binding Targets.
N. S. Belaguli, W. Zhou, T.-H. T. Trinh, M. W. Majesky, and R. J. Schwartz (1999)
Mol. Cell. Biol. 19, 4582-4591
   Abstract »    Full Text »    PDF »
The Wilms' Tumor Suppressor, WT1, Inhibits 12-O-Tetradecanoylphorbol-13-acetate Activation of the Multidrug Resistance-1 Promoter.
C. McCoy, S. B. McGee, and M. M. Cornwell (1999)
Cell Growth Differ. 10, 377-386
   Abstract »    Full Text »
Tumor-associated WT1 Missense Mutants Indicate That Transcriptional Activation by WT1 Is Critical for Growth Control.
M. A. English and J. D. Licht (1999)
J. Biol. Chem. 274, 13258-13263
   Abstract »    Full Text »    PDF »
WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes.
R. C. Davies, C. Calvio, E. Bratt, S. H. Larsson, A. I. Lamond, and N. D. Hastie (1998)
Genes & Dev. 12, 3217-3225
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Expression of the Wilms' Tumor Suppressor Gene, WT1, Is Upregulated by Leukemia Inhibitory Factor and Induces Monocytic Differentiation in M1 Leukemic Cells.
S. I. Smith, D. Weil, G. R. Johnson, A. W. Boyd, and C. L. Li (1998)
Blood 91, 764-773
   Abstract »    Full Text »    PDF »
Differential Function of Wilms' Tumor Gene WT1 Splice Isoforms in Transcriptional Regulation.
S. M. Hewitt, G. C. Fraizer, Y.-J. Wu, F. J. Rauscher III, and G. F. Saunders (1996)
J. Biol. Chem. 271, 8588-8592
   Abstract »    Full Text »    PDF »
Expression of the Three Alternative Forms of the Sphingolipid Activator Protein Precursor in Baby Hamster Kidney Cells and Functional Assays in a Cell Culture System.
M. Henseler, A. Klein, G. J. Glombitza, K. Suziki, and K. Sandhoff (1996)
J. Biol. Chem. 271, 8416-8423
   Abstract »    Full Text »    PDF »
The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis..
S Maheswaran, C Englert, P Bennett, G Heinrich, and D A Haber (1995)
Genes & Dev. 9, 2143-2156
   Abstract »    PDF »
Repression of Pax-2 by WT1 during normal kidney development.
G Ryan, V Steele-Perkins, J. Morris, F. Rauscher, and G. Dressler (1995)
Development 121, 867-875
   Abstract »    PDF »
A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
Y Miki, J Swensen, D Shattuck-Eidens, P. Futreal, K Harshman, S Tavtigian, Q Liu, C Cochran, L. Bennett, W Ding, et al. (1994)
Science 266, 66-71
   Abstract »    PDF »
RNA editing in the Wilms' tumor susceptibility gene, WT1..
P M Sharma, M Bowman, S L Madden, F J Rauscher, and S Sukumar (1994)
Genes & Dev. 8, 720-731
   Abstract »    PDF »
WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
D. Haber, S Park, S Maheswaran, C Englert, G. Re, D. Hazen-Martin, D. Sens, and A. Garvin (1993)
Science 262, 2057-2059
   Abstract »    PDF »
Multiple zinc finger forms resulting from developmentally regulated alternative splicing of a transcription factor gene.
T Hsu, J. Gogos, S. Kirsh, and F. Kafatos (1992)
Science 257, 1946-1950
   Abstract »    PDF »
The Zinc Finger Domain of Tzfp Binds to the tbs Motif Located at the Upstream Flanking Region of the Aie1 (aurora-C) Kinase Gene.
C.-J. C. Tang, C.-K. Chuang, H.-M. Hu, and T. K. Tang (2001)
J. Biol. Chem. 276, 19631-19639
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Molecular genetics of chromosome translocations involving EWS and related family members.
J. KIM and J. PELLETIER (1999)
Physiol Genomics 1, 127-138
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