Promoter region of the human pro-alpha 1(II)-collagen gene.

We have isolated a genomic clone containing the 5'-terminal portion of the human pro-alpha 1(II)-collagen gene. This clone, HC2C, contains 10 kb of the gene and 6 kb of 5'-flanking sequences. It was selected by cross hybridization using a [32P]DNA probe containing the promoter region of the rat alpha 1(II)-collagen gene. We have determined the nucleotide sequence of the first exon and of 400 bp upstream. There is considerable homology between this human sequence and the corresponding rat sequence. As in the rat, the first exon contains a 155-bp untranslated segment and a 85-bp sequence coding for the signal peptide and a part of the N-propeptide of type-II procollagen. The segment preceding the transcription initiation site contains a conserved 'ATATAA' element, and several similar G + C-rich stretches. As in the rat gene, no 'CAT' element is evident between -70 and -120. We also find the sequence 5'-GTGGTCAGA-3' reported as an enhancer element in both viral and cellular genes, located around -290 bp. A high degree of homology exists between the atypical rat and human promoter structures; however, such homology is absent among the alpha 1(I), alpha 2(I) and alpha 1(III) promoters, which suggests that the unique alpha 1(II) sequences may be related to the specific expression of the alpha 1(II)-collagen gene.