Positive and negative feedback loops affect the transcription of IME1, a positive regulator of meiosis in Saccharomyces cerevisiae

Abstract
The IME1 gene of Saccharomyces cerevisiae encodes a transcription factor that is required for the expression of meiosis-specific genes. Like many of the genes it regulates, IME1 itself is expressed according to the following complex pattern: barely detectable levels during vegetative growth, and high induced levels under starvation conditions, followed by a subsequent decline in the course of meiosis. This report examines the influence of Ime1 protein on its own expression, demonstrating feedback regulation. Disruption of either IME1 or IME2 leads to constantly increasing levels of Ime1-lacZ expression, under meiotic conditions. This apparent negative regulation is due to cis elements in the IME1 upstream region, which confer transient meiotic expression to heterologous promoter-less genes. A specific DNA/protein complex, whose level is transiently increased under meiotic conditions, is detected on this element. In ime1 diploids, the level of this DNA/protein complex increases, without any decline. These results indicate that the transient expression of IME1 is apparently due to transcriptional regulation. This report also presents evidence suggesting that Ime 1p is directly responsible for regulating its own transcription. Positive feedback regulation in mitotic conditions is suggested by the observation that overexpression of Ime 1p leads to increased levels of IME1-lacZ. Negative autoregulation in meiotic cultures is demonstrated by the observation that a specific point mutation in IME1, ime 1–3, permits expression of meiosis-specific genes, as well as induction of meiosis, but is defective in negative-feedback regulation of IME1.