The alpha6 integrin subunit couples with either the @entity8652 or the beta4 subunit to form a laminin receptor. alpha6 expression is cell-type-specific and generally is present at high levels in epithelial and endothelial cells. To study its gene regulation, we isolated a genomic clone containing the @entity1 alpha6 integrin gene promoter. It includes 3 kb of the upstream flanking region, the first exon (385 bp), and 9 kb of the first intron. The alpha6 promoter directs transcription initiation from a primary site 202 nucleotides from the translation initiation codon. Unlike most other integrin gene promoters, the alpha6 promoter has a TATA box (GATAAA), which is located 22 @entity2036 upstream from the primary transcription initiation site. A 190-bp region upstream from the TATA box is highly rich (78%) in C and G nucleotides and contains several @entity3419 and @entity18720 binding sequences. However, full promoter activity (in the presence of the SV40 enhancer) requires only 78 bp of this C/G-rich sequence upstream from the TATA box. Slightly upstream from the C/G-rich region are a @entity134 receptor binding homolog and an epithelial-cell-specific E-pal sequence. Another possible epithelial cell-specific binding sequence (Ker1) is found immediately downstream from the TATA box. Cell-type-specific activities of the promoter paralleled the alpha6 mRNA levels in four tested cell lines. In the presence of the SV40 enhancer, alpha6 promoter activity increased approximately four-fold in primary keratinocytes and in HT1080 @entity1492 cells and 30-fold in T47D @entity0 cells, but remained undetectable in K562 @entity1778 cells. Genomic analysis that compared alpha6-expressing with non-alpha6-expressing cells suggested that DNA methylation is not involved in the silencing of the alpha6 gene in alpha6-negative cells. DNase I footprint analysis confirmed the binding of @entity3419 and @entity18720 to their cognate sequences. A nuclear extract of high-alpha6-expressing @entity1 cells also produced significant binding to these sites, suggesting that the two transcription factors are probably involved in the positive regulation of the alpha6 promoter.

Identification of the XXXX alpha6 integrin gene promoter.

@entity1 :: ('9606', 'Species') :: ['human', 'HBL-100'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast carcinoma'] @entity2036 :: ('MESH:D009711', 'Chemical') :: ['nucleotides'] @entity8652 :: ('3779', 'Gene') :: ['beta1'] @entity1492 :: ('MESH:D005354', 'Disease') :: ['fibrosarcoma'] @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia'] @entity3419 :: ('6667', 'Gene') :: ['Sp1'] @entity18720 :: ('7020', 'Gene') :: ['AP2']
@entity1 :: (9606,Species) :: ['human']
