Gene regulation in microbial eukaryotes in the early 1990s

Abstract

Just as studies in earlier decades of gene regulation in mutagenesis and expression studies with the corresponding prokaryotes provided paradigms for mechanisms of gene mutant vertebrate transcription factors. Another specificity regulation in all organisms, so studies with microbial mutation of the Aspergillus nitrogen regulatory gene is a eukaryotes will provide important insights into the control duplication of the entire DNA-binding region (Caddick & of gene expression in all eukaryotes. For example, provided . ,Arsf, in press). This didactylous mutant raises a number of appropriate cis-acting receptor sites are adjacent to structural interesting points of which one is whether it can regulate genes, the yeast GAL4 regulatory gene product can activate expression of any genes not regulated by the wild type structural gene expression not only in yeast cells but als0 ~ form Of the regulatory gene product. From an evolutionary in insect (Fischer et al. 1988), plant (Ma et al. 1988) and point Of view the intriguing point is that the erythroid mammalian (Kakidani & Ptashne 1988; Webster et al. 1988) cells. The similarities of its action in yeast and higher eukaryotic cells are underlined by the fact that mutations which increase its effectiveness in yeast cells also do so in mammalian cells (Gill el al. 1990). Still further evidence for the commonality of regulatory mechanisms across a broad evolutionary range comes from domain-swapping experiments involving another yeast transcriptional activator, GCN4, and mammalian proto-oncogene products (Sellers & Struhl 1989). There is also evidence that DNA-binding motifs can predate the evolutionary divergence of fungi and animals, a divergence which, in the case of filamentous fungi, might be more recent than that ~with yeasts (Smith 1989). A putative 'zinc finger' and adjacent residues show extraordinary conservation between a filamentous fungal gene product involved in the regulation of nitrogen acquisition and the major DNA-binding protein of the vertebrate erythroid cell lineage, the tissue-specific regulator of, inter alia, globin biosynthesis (Arst eta]. 1989; Fu & Marzluf 1990; Kudla et aI. I990). Of particular interest are mutations affecting a leucine residue in the 'zinc finger' loop which is conserved throughout all 'fingers' of this class. Two Aspergillus specificity mutations having approximately reciprocal or 'mirror image' phenotypes change this residue to valine and methionine, respectively (Kudla et al. 1990). Thus the fungal work literally cries out for in vitro