Regulation of expression of the alpha 1 (I) collagen gene: A critical appraisal of the role of the first intron

The transcriptional regulation of the genes encoding the alpha 1 (I) and alpha 2 (I) collagen chains is necessarily complex since these genes are expressed at widely different levels, and in a cell- and tissue-specific fashion. In the case of the alpha 1 (I) gene, there is substantial, but controversial, evidence for an involvement of the first intron in the tissue-specific expression of the gene. This evidence is based largely on transfection of cells with collagen-reporter gene constructs and on studies of transgenic mice. In this review, I propose a number of reasons for the conflicting data in the literature: 1) the cell-specific nature of the intronic effect; thus, not all cultured, collagen-synthesizing cells will demonstrate an intronic effect by transfection; 2) the possibility that functionally equivalent regulatory elements are placed in different regions of the alpha 1 (I) gene in different species; and 3) the possibility that functionally redundant sequences exist within the alpha 1 (I) gene, which would permit other regions to substitute for the first intron.