REGULATION OF EXPRESSION OF THE TYPE-I COLLAGEN GENES

The identification and functional analysis of DNA-protein interactions in the intronic and 5' flanking regions of the type I collagen genes has begun to define a series of cis-elements and trans-acting factors which regulate transcription of these genes. Studies such as these will eventually be expected to elucidate the mechanisms responsible for coordinate transcription of the alpha1 and alpha2 genes, a question which remains central to the field of collagen research. Although it is relatively straightforward to define sites of DNA-protein binding, interpretation of the functional importance of such interactions can be extremely complex. Furthermore, while mutation or deletion of a particular binding site may alter the functional activity of a construct transfected into cultured cells, there is no guarantee that a similar change will have the same effect in vivo, where the entire gene locus is present in its native chromosomal context. Nevertheless, these kinds of in vitro studies offer the best current approach to defining and isolating transcription factors that control expression of the alpha1 and alpha2 genes. Ultimately, it will be necessary to test the activity of such factors (and their respective cis-elements) in defined systems in vivo.