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) a nd alpha 2 (I) collagen chains is necessarily complex since these gene s 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 substa ntial, but controversial, evidence for an involvement of the first int ron in the tissue-specific expression of the gene. This evidence is ba sed largely on transfection of cells with collagen-reporter gene const ructs and on studies of transgenic mice. In this review, I propose a n umber of reasons for the conflicting data in the literature: 1) the ce ll-specific nature of the intronic effect; thus, not all cultured, col lagen-synthesizing cells will demonstrate an intronic effect by transf ection; 2) the possibility that functionally equivalent regulatory ele ments are placed in different regions of the alpha 1 (I) gene in diffe rent species; and 3) the possibility that functionally redundant seque nces exist within the alpha 1 (I) gene, which would permit other regio ns to substitute for the first intron.