Integrator gene in Aspergillus nidulans

Abstract

ONE of the most intriguing problems in genetics is how the regulation of a particular structural gene can be programmed in such a way that its expression can be elicited in a variety of different contexts. Stated differently, how can the concomitant expression of two or more non-contiguous structural genes capable of independent expression be achieved? Britten and Davidson^1–3 have proposed a model for gene regulation which gives considerable insight into this problem. One feature of their model is the existence of positively acting regulatory genes, designated integrator genes, whose role is to achieve precisely this concomitant expression of non-contiguous structural genes. Although the model was developed to account for cell differentiation in higher eukaryotes, a similar, although possibly less elaborate, form of regulatory machinery might be applicable in lower eukaryotes. In the fungus Aspergillus nidulans, as in higher eukaryotes, functionally related genes are seldom clustered⁴. Given the considerable metabolic versatility of this organism, instances of inducible enzymes participating in more than one metabolic pathway should not be unduly rare. Evidence for the existence of integrator genes could come from the study of regulatory mutations affecting such enzymes. The model also requires the existence of receptor sites for integrator gene products, a not implausible requirement for A. nidulans, where several cis-acting regulatory mutations tightly linked to structural genes under their control have been identified (refs 5–8 and unpublished results of C. R. Bailey and H. N. A.). Here I report that the intAgene of A.nidulans, previously designated amdR and shown by Hynes and coworkers^9–11 to be a positive regulatory gene in linkage group II involved in acetamidase synthesis, is an integrator gene of the type described by Britten and Davidson. Moreover, intA is possibly especially interesting because one of the compounds whose metabolism it controls is γ-amino-n-butyric acid (GABA), whose metabolism has been extensively investigated in a wide variety of organisms because of its role in the regulation of neuronal activity.