A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant.

Epstein, Douglas J.; Vogan, Kyle; Trasler, Daphne G.; Gros, Philippe

doi:10.1073/pnas.90.2.532

Cited by 167 publications

(110 citation statements)

References 35 publications

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“…The expression pattern ofPax-3 suggests that it plays an important role in the regional specification of certain aspects of the nervous system. Recently, this hypothesis has been confirmed as mutations in the Pax-3 gene were found to be responsible for the splotch (sp) phenotype in mice (2)(3)(4)(5) and the Waardenburg syndrome type 1 (WS1) in humans (6)(7)(8)(9)(10). Furthermore, a chromosomal translocation of PAX3 (the human homolog of mouse Pax-3; ref.…”

mentioning

confidence: 76%

Pax-3 contains domains for transcription activation and transcription inhibition.

Chalepakis

Jones

Edelman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

124

100

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Pax-3 is a member of the Pax family of transcription factors involved in transcriptional control events during embryonic development. Here we report a functional dissection of the Pax-3 protein and describe the protein domains which are responsible for different activities. A transcription inhibition activity is located in the rst 90 N-terminal amino acids and includes part of the paired domain. Furthermore, the C terminus of Pax-3 is able to confer transcriptional activation of basal promoters. Pax-3 can utilize both transcription modulating functions and activates transcription over a narrow range of protein concentration in the presence of promoter elements containing functional binding sites.

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mentioning

confidence: 76%

Pax-3 contains domains for transcription activation and transcription inhibition.

Chalepakis

Jones

Edelman

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

124

100

View full text Add to dashboard Cite

show abstract

“…In mice, the spontaneous Pax3 mutation Splotch causes the lack of limb muscles, spina bifida and exencephaly, and defects in neural crest derivatives (27). Human patients with impaired Pax3 function suffer from Waardenburg syndrome (28), a disease complex characterized by varying degrees of deafness, defects in structures arising from the neural crest, and pigmentation anomalies.…”

Section: Discussionmentioning

confidence: 99%

T-box Protein Tbx18 Interacts with the Paired Box Protein Pax3 in the Development of the Paraxial Mesoderm

Farin

Mansouri

Petry

et al. 2008

Journal of Biological Chemistry

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The compartmentalization of somites along their anteriorposterior axis is crucial to the segmental organization of the vertebral column. Anterior-posterior somite polarity is generated in the anterior presomitic mesoderm by Mesp2 and Delta/ Notch signaling and is further maintained by two transcriptional regulators, Uncx4.1 and Tbx18, acting in the posterior and anterior somite compartment, respectively. Here, we report that the paired box transcription factor Pax3 cooperates with the T-box protein Tbx18 in maintaining anterior somite half identity. Our findings that both genes are co-expressed in the anterior presomitic mesoderm and in early somites, that Pax3 and Tbx18 proteins physically interact, and that the loss of Pax3 gene function enhances the vertebral defects (i.e. the gain of vertebral elements derived from posterior somite halves in Tbx18 mutant mice) suggests that the two proteins cooperatively regulate the gene expression program necessary for maintaining anterior-posterior somite polarity. Genetic interaction of Pax3 with Tbx18 and the closely related T-box gene Tbx15 was also observed in the development of the scapula blade, indicating an additional cooperative function for these genes in the paraxial mesoderm.

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“…The mouse undulated phenotype is correlated with mutations in Par-i (6, 7), the mouse small eye (8) and the human aniridia have been correlated with mutations in the Pax-6 gene (9)(10)(11). been associated with the splotch phenotype in mouse (12)(13)(14)(15) and the Waardenburg syndrome in man (16)(17)(18)(19)(20). A chromosomal translocation of PAX3 (the human homolog of the mouse Pax-3, ref.…”

Section: Introductionmentioning

confidence: 99%

Pax-3-DNA interaction: flexibility in the DNA binding and induction of DNA conformational changes by paired domains

Chalepakis

Wijnholds²,

Gruß

1994

Nucl Acids Res

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The mouse Pax-3 gene encodes a protein that is a member of the Pax family of DNA binding proteins. Pax-3 contains two DNA binding domains: a paired domain (PD) and a paired type homeodomain (HD). Both domains are separated by 53 amino acids and interact synergistically with a sequence harboring an ATTA motif (binding to the HD) and a GTTCC site (binding to the PD) separated by 5 base pairs. Here we show that the interaction of Pax-3 with these two binding sites is independent of their angular orientation. In addition, the protein spacer region between the HD and the PD can be shortened without changing the spatial flexibility of the two DNA binding domains which interact with DNA. Furthermore, by using circular permutation analysis we determined that binding of Pax-3 to a DNA fragment containing a specific binding site causes conformational changes in the DNA, as indicated by the different mobilities of the Pax-3 -DNA complexes. The ability to change the conformation of the DNA was found to be an intrinsic property of the Pax-3 PD and of all Pax proteins that we tested so far. These in vitro studies suggest that interaction of Pax proteins with their specific sequences in vivo may result in an altered DNA conformation.

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A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant.

Abstract: The splotch (Sp) mouse mutant displays de-

Cited by 167 publications

References 35 publications

Pax-3 contains domains for transcription activation and transcription inhibition.

Pax-3 contains domains for transcription activation and transcription inhibition.

T-box Protein Tbx18 Interacts with the Paired Box Protein Pax3 in the Development of the Paraxial Mesoderm

Pax-3-DNA interaction: flexibility in the DNA binding and induction of DNA conformational changes by paired domains

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