| First Author | Okladnova O | Year | 1999 |
| Journal | Genomics | Volume | 57 |
| Issue | 1 | Pages | 110-9 |
| PubMed ID | 10191090 | Mgi Jnum | J:54667 |
| Mgi Id | MGI:1335685 | Doi | 10.1006/geno.1998.5711 |
| Citation | Okladnova O, et al. (1999) Functional characterization of the human PAX3 gene regulatory region. Genomics 57(1):110-9 |
| abstractText | 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. Copyright 1999 Academic Press. |
