Molecular mechanisms of collagen gene expression

Collagens are a structurally and functionally heterogenous group of proteins encoded by a family of genes that share evolutionary history. Collagen gene expression is regulated both in developmental, tissue-specific manners as well as in response to a variety of biologic and pharmacologic inducers. In the present review we have attempted to synthesize a conceptual overview of the available information from studies aimed at deciphering the molecular mechanisms of collagen gene expression. We have chosen to focus our discussion mainly, although not exclusively, to observations relating to type I collagen gene for a number of practical reasons. The underlying theme that emerges from this survey of the literature is that the regulation of collagen gene expression is complex, utilizing transcriptional, posttranscriptional and translational mechanisms. Although the transcriptional control mechanisms that involve activation and modulation of collagen gene transcription by RNA polymerase II appear to predominate, preferential stabilization of collagen mRNAs and modulation of translational discrimination appear to play significant roles in the regulation of collagen biosynthesis under some physiological situations. Molecular organization of the regulatory regions of collagen genes reveal a mosaic of subdomains with overlapping sequence motifs, involved in positive and negative transcriptional regulation. The precise identity of the cis-acting subdomains of the promoter/enhancer-proximal DNA of collagen gene and how they interact with the trans-acting nuclear protein(s) have yet to be elucidated and will remain the focus of future studies.