Functional characterization of the human PAX3 gene regulatory region

Genomics. 1999 Apr 1;57(1):110-9. doi: 10.1006/geno.1998.5711.


Spatiotemporal expression of the PAX3 gene is tightly regulated during development. We have isolated and sequenced the 5'-flanking regulatory region of human PAX3. Primer extension and ribonuclease protection mapping revealed that transcription is initiated from a single start site downstream of a TATA-like motif in human brain and peripheral tissues. Functional dissection of the gene's 5'-flanking region, which had been fused to a luciferase reporter gene and transiently expressed in rhabdomyosarcoma (RD) and cos-7 cells, indicated that the upstream region of PAX3 contains multiple positive and negative cis-acting regulatory elements. While the basal promoter is likely to be driven by two CCAAT boxes located at nucleotide positions -90 and -135, a cluster of regulatory elements acting as a strong repressor was detected between nucleotides -1200 and -650. Comparison of human and murine sequences revealed more than 90% identity in this segment. A polymorphic (CA)n repeat sequence and a G/C substitution are located 337 bp and 328 bp upstream of the transcription start site, respectively. PCR-based systematic screening for length variations in 225 unrelated individuals of a Caucasian population showed a bimodal distribution of multiple alleles containing between 13 and 30 repeat units. Although the (CA)25 variant of this PAX3 gene-linked polymorphic region (PAX3LPR) conferred lower transcriptional efficiency on the PAX3 promoter, a regulatory impact of the PAX3LPR on PAX3 expression related to brain plasticity and function remains to be demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells / metabolism
  • DNA-Binding Proteins / genetics*
  • Dinucleotide Repeats
  • Gene Library
  • Genes, Regulator / genetics*
  • Genes, Reporter
  • Genotype
  • Humans
  • Luciferases / metabolism
  • Models, Genetic
  • Molecular Sequence Data
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Plasmids
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Rhabdomyosarcoma / metabolism
  • Ribonucleases / metabolism
  • Sequence Homology, Nucleic Acid
  • Tissue Distribution
  • Transcription Factors*
  • Transcription, Genetic
  • Transfection


  • DNA-Binding Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors
  • Pax3 protein, mouse
  • Luciferases
  • Ribonucleases

Associated data

  • GENBANK/AJ007392