Autoregulation of GAL4 transcription is essential for rapid growth of Kluyveromyces lactis on lactose and galactose.

Transcriptional induction of genes in the lactose-galactose regulon of the yeast Kluyveromyces lactis requires the GAL4 transcription activator protein. Previous data indicated that the concentration of GAL4 was tightly regulated under basal, inducing, and glucose repressing conditions but the mechanisms were unknown. In this paper we demonstrate that transcription of the GAL4 gene (KI-GAL4) increases 3- to 4-fold during induction of the regulon. This increase requires a KI-GAL4 binding site, UASG, in front of the KI-GAL4 gene, indicating that the KI-GAL4 protein autoregulates transcription of its own gene. Our data demonstrate that the autoregulatory circuit is essential for full induction of the lactose-galactose regulon and, hence, for rapid growth on lactose or galactose. Other data indicate that basal transcription of the KI-GAL4 gene is governed by unidentified promoter elements. The existence of the autoregulatory circuit reveals an important difference between the lactose-galactose regulon and its homologue in Saccharomyces cerevisiae, the melibiose-galactose regulon. This difference may have evolved in response to different selective pressures encountered by the two organisms.