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Structural and functional analysis of the first intron of the human alpha 2(I) collagen-encoding gene.

The nucleotide (nt) sequence of the first intron of the human alpha 2(I) collagen-encoding gene (COL1A2) has been determined from its 5' terminus (nt 207) to nt 2045 with respect to the transcription start point. Although the first intron contains elements known to function in transcriptional regulation of other genes (two AP1-binding sites and an alternating GT stretch), comparison of this sequence with that of the mouse COL1A2 first intron revealed a low degree of nt sequence identity and very few common DNA-protein binding motifs. In keeping with this structural analysis, the human intron was found to inhibit COL1A2 promoter activity in transfection experiments, whereas a strong enhancer was reported to be present in the first intron of mouse COL1A2 [Rossi and deCrombrugghe, Proc. Natl. Acad. Sci. USA 84 (1987) 5590-5594]. We conclude that the high degree of nt sequence conservation existing in the promoter and first exons of human, mouse and chicken COL1A2 does not extend to the first introns of these genes but that the promoter activity of COL1A2 is strongly influenced by the presence of the first intron.