The adhesive proteins in the desmosome type of cell junction consist of two members of the cadherin superfamily, the desmogleins and desmocollins. Both desmogleins and desmocollins occur as at least three different isoforms with various patterns of expression. The molecular mechanisms controlling the differential expression of the desmosomal cadherin isoforms are not yet known. We have begun an investigation of desmoglein gene expression by cloning and analysing the promoters of the @entity1 genes coding for the type 1 and type 3 desmogleins ( @entity7620 and @entity8260 ). The type 1 isoform is restricted to the suprabasal layers of the epidermis and is the autoantigen in the autoimmune blistering @entity272 pemphigus foliaceous. The type 3 desmoglein isoform is also expressed in the epidermis, but in lower layers than the type 1 isoform, and is the autoantigen in @entity7271 . @entity5999 genomic clones were obtained containing 4.2 kb upstream of the translation start site of @entity7620 and 517 bp upstream of the @entity8260 start site. Sequencing of 660 bp upstream of @entity7620 and 517 bp upstream of @entity8260 revealed that there was no obvious TATA box, but a possible CAAT box was present at -238 in @entity7620 and at -193 in @entity8260 relative to the translation start site. Primer extension analysis and RNase protection experiments revealed four putative transcription initiation sites for @entity7620 at positions -163, -151, -148 and -141, and seven closely linked sites for @entity8260 , the longest being at -140 relative to the translation start site. The sequences at these possible sites at -166 to -159 in @entity7620 (TTCAGTCC) and at -124 to -117 in @entity8260 (CTTAGACT) have some similarity to the initiator sequence (CTCANTCT) described for a TATA-less promoter often from -3 to +5, and the true transcription initiator site might therefore be the A residue in these sequences. There were two regions of similarity between the @entity7620 and @entity8260 promoters just upstream of the transcription initiation sites, of 20 and 13 bp, separated by 41 bp in @entity7620 and 36 bp in @entity8260 . The significance of these regions of similarity remains to be elucidated, but the results suggest that they represent a point at which these two desmoglein genes are co-ordinately regulated. Analysis of the upstream sequences revealed GC-rich regions and consensus binding sites for transcription factors including @entity1178 and @entity18720 . Exon boundaries were conserved compared with the classical cadherin E-cadherin, but the equivalent of the second cadherin intron was lacking. A 4.2 kb region of the @entity1 @entity7620 promoter sequence was linked to the lacZ gene reporter gene in such a way that there was only one translation start site, and this construct was used to generate @entity19 . We present the first transgenic analysis of a promoter region taken from a desmosomal cadherin gene. Our results suggest that the 4.2 kb upstream region of @entity7620 does not contain all the regulatory elements necessary for correct expression of this gene but might have elements that regulate activity during hair growth.

Characterization of the regulatory regions in the @entity1 desmoglein genes encoding the pemphigus foliaceous and XXXX antigens.

@entity1 :: ('9606', 'Species') :: ['human'] @entity8260 :: ('1830', 'Gene') :: ['DSG3'] @entity7271 :: ('MESH:D010392', 'Disease') :: ['pemphigus vulgaris'] @entity19 :: ('10090', 'Species') :: ['transgenic mice'] @entity5999 :: ('10710', 'Species') :: ['Phage lambda'] @entity1178 :: ('3725', 'Gene') :: ['AP-1'] @entity7620 :: ('1828', 'Gene') :: ['DSG1'] @entity272 :: ('MESH:D012871', 'Disease') :: ['skin disease'] @entity18720 :: ('7020', 'Gene') :: ['AP-2']
@entity7271 :: (MESH:D010392,Disease) :: ['pemphigus vulgaris']
