Molecular mechanisms involved in the regulation of gene expression during cell differentiation and development

Abstract

One general point to emerge from this review is that each step in the pathway for gene expression from DNA to final polypeptide via chromosome structure, primary transcript, mRNA processing, stability, and translation is exploited in some developmental context as a means of regulation. Moreover, there is little evidence that the regulation of different stages in this pathway is associated consistently with particular classes of genes or developmental processes: for example, homeotic and other regulatory genes, which are important in early development and in determining the overall structures of organisms, are regulated by both transcriptional and posttranscriptional mechanisms, as are many other genes encoding cell-type-specific proteins expressed late during terminal differentiation. There are also instances in which transcription factors regulating tissue-specific transcription are present constitutively but are activated only in certain cell types by posttranslational events, and in yeast, coordinate regulation of amino-acid biosynthesis genes involves the translation control of a transcription factor. Second, as far as transcriptional control is concerned, it is now clear that in most instances cell-type specificity arises from the activities of multiple cis-control elements that can act either positively or negatively: The precise way in which the gene functions depends on what combination of cis-control elements it possesses. A third somewhat negative point is that in general the mechanisms responsible for the coordinate expression of genes during cell differentiation and development are not yet understood. In view of the complexities of possible mechanisms noted above, it may be that closely related genes (such as those encoding the alpha- and beta-globins, for example) in fact come to be coordinately expressed via a complex, indirect route. Indeed, it is quite possible that such mechanisms will not be revealed simply by a reductionist approach studying relatively short regions of DNA and that some form of overall "systems analysis" will be required. Finally, what we know relates mainly to expression of genes within particular cell types. How groups of cells are organized into complex structures remains a mystery at the molecular level, although progress into the genetic principles involved in the regulation of such "compartments" is being made, mainly in insects, reviewed recently by Brower, although to some extent also in the mouse [discussed by Hogan and co-workers].