title: Transcriptional regulation of the human PAX6 gene promoter.
abstract: PAX6, a member of the highly conserved paired-type homeobox gene family, is expressed in a spatially and temporally restricted pattern during early embryogenesis, and its mutation is responsible for human aniridia. Here we examined the transcriptional regulation of the PAX6 gene by transient transfection assays and identified multiple cis-regulatory elements that function differently in different cell lines. The transcriptional initiation site was identified by RNase protection and primer extension assay. Examination of the genomic DNA sequence indicated that the PAX6 promoter has a TATA like-box (ATATTTT) at -26 base pairs (bp), and two CCAAT boxes are positioned at -70 and -100 bp. A 38-bp poly(CA) sequence was located 992 bp upstream from the initiation site. Transient transfection assays in glioblastoma cells and leukemia cells indicate that a 92-bp region was required for basal level PAX6 promoter activity. A negative transcriptional element, silencer (bases -1518 to -1268), functioned differently in different cell lines. The activation of the promoter is positively correlated with the expression of PAX6 transcripts in all cells tested. These results indicate that a cis-regulatory element or elements is responsible for selective activation of the PAX6 promoter in cells that can express PAX6 mRNA.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Xu
authors.forename: G F
authors.initials: GF
authors.lastname: Saunders
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D005136:Eye Proteins; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors