Characterization of the Mouse Gene for the α1 Chain of Type XVIII Collagen (Col18a1) Reveals That the Three Variant N-Terminal Polypeptide Forms Are Transcribed from Two Widely Separated Promoters

Abstract The mouse gene for the α1 chain of type XVIII collagen ( Col18a1 ) is more than 102 kb and consists of 43 exons. Type XVIII collagen transcripts encode polypeptides that differ with respect to three variant N-terminal noncollagenous domains that are 301 (NC1-301), 517 (NC1-517), or 764 (NC1-764) residues in length. Characterization of genomic clones revealed that the three variant NC1 domains result from the use of two alternative promoters, separated by a distance of 50 kb. The upstream promoter, promoter 1, directs the synthesis of the NC1-301 domain in conjunction with exons 1 and 2, whereas the downstream promoter, promoter 2, directs that of the NC1-517 and NC1-764 domains in conjunction with exon 3, with the latter two variants differing with respect to alternative splicing of the exon 3 sequences. Exons 4–9 encode a portion of the NC1 domain shared by all three polypeptide variants, and exons 9–43 encode the common collagenous and C-terminal noncollagenous sequences. The marked differences previously observed in the expression of variant type XVIII collagen transcripts in mouse tissues thus result from tissue-specific use of these two promoters.