A promoter-associated polymorphic repeat modulates PAX-6 expression in human brain

Biochem Biophys Res Commun. 1998 Jul 20;248(2):402-5. doi: 10.1006/bbrc.1998.8972.


The PAX-6 gene plays a critical role in neurodevelopment and brain plasticity. While transcription of human PAX-6 is regulated by alternate usage of two distinct promoters termed A and B, expression in adult human brain is primarily controlled by promoter B. We now report that a novel polymorphic dinucleotide repeat sequence with the structure (AC)m(AG)n is located approximately 1 kb upstream of the transcription initiation site associated with promoter B. PCR-based systematic screening for length variations in a caucasian population showed a skewed distribution of multiple alleles containing between 24 and 36 repeat units. In 217 unrelated individuals, the frequency of alleles in the range between 25 and 29 repeats was 90%, with the 26 repeat allele alone accounting for 50%; the heterozygosity rate was 65%. Variants of this PAX-6 gene-linked polymorphic region (PAX-6LPR) had different transcriptional efficiencies when fused to a luciferase reporter gene and transfected into Cos-7 cells. Promoter activity of variants with >/=29 repeats was 4- to 9-fold higher than that of the 26 repeat allele. The influence of the PAX-6LPR on PAX-6 expression was confirmed in postmortem cerebellum from individuals with different genotypes. mRNA levels were 2-fold higher in genotypes with long alleles compared to those with short alleles. Allelic variation in PAX-6 expression may be a determinant of interindividual differences in brain plasticity and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Brain / physiology*
  • DNA-Binding Proteins / genetics*
  • Dinucleotide Repeats / genetics*
  • Eye Proteins
  • Gene Expression Regulation / genetics*
  • Genes, Reporter / genetics
  • Homeodomain Proteins*
  • Humans
  • Nerve Tissue Proteins / genetics
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / metabolism
  • Repetitive Sequences, Nucleic Acid / genetics
  • Repressor Proteins
  • Whites


  • DNA-Binding Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • RNA, Messenger
  • Repressor Proteins