Conservation of Binding Sites for Regulatory Factors in the Coordinately Expressed Alpha 1 (I) and Alpha 2 (I) Collagen Promoters

To examine possible mechanisms for the coordinate control of the alpha 1 (I) and alpha 2 (I) collagen genes, we have searched for DNA binding factors that are common to both genes. We have recently identified in the proximal part of the alpha 1 (I) promoter a functional binding site for CBF, a heteromeric transcriptional activator which binds to certain CCAAT sequences, and also functional binding sites for two different transcriptional repressors, designated IF1 and IF2. CBF was previously also shown to bind and activate the alpha 2(I) collagen promoter. We now present evidence that a factor with similar binding characteristics as IF1 binds to the alpha 2(I) promoter at approximately the same distances from the start site of transcription as in the alpha 1(I) collagen promoter. A three bp substitution mutation in the IF1 binding site which abolishes IF1 binding increases the activity of the alpha 2(I) promoter 4-fold as with the alpha 1 (I) promoter. We propose that the coordinate regulation of these two genes is at least in part mediated by these common elements.