Transcriptional regulation of the human type I collagen alpha2 (COL1A2) gene by the combination of two dinucleotide repeats.

Human type I collagen alpha2 (COL1A2) gene has two dinucleotide repeats: one in the 5'-flanking region of the gene is composed of poly(dC-dA) and poly(dC-dG), while the other in the first intron consists of poly(dG-dT). In this study, we show that transcription of the COL1A2 gene is regulated by these repeats. Luciferase reporter gene assay indicated that the transcriptional activity of the COL1A2 gene was enhanced by the co-presence of both repeats, but not by either repeat alone. Analysis of the polymorphism in the two repeat regions indicated that both sequences have a variation in their repetition number, thus showing that these dinucleotide repeats constitute microsatellites. A study using constructs containing various combinations of the repeat alleles showed differences in their transcriptional activities. The results, however, showed that the stimulation rate of luciferase activity was not linear with the repetitive number of the repeats either in the 5' flanking region or in the first intron of the gene and that the stimulation was provided by the combination of these polymorphic repetitive sequences. These observations indicated that the dinucleotide repeats have an enhancing activity on transcription of the COL1A2 gene and that the variation in the number of repetitions may partly be responsible for the difference in the transcriptional activity of the gene.