The Transcriptional Regulator Ume6 is a Major Driver of Early Gene Expression during Gametogenesis.

Abstract

The process of gametogenesis is orchestrated by a dynamic gene expression program, where a vital subset constitutes the early meiotic genes (EMGs). In budding yeast, the transcription factor Ume6 represses EMG expression during mitotic growth. However, during the transition from mitotic to meiotic cell fate, EMGs are activated in response to the transcriptional regulator Ime1 through its interaction with Ume6. While it is known that binding of Ime1 to Ume6 promotes EMG expression, the mechanism of EMG activation remains elusive. Two competing models have been proposed whereby Ime1 either forms an activator complex with Ume6 or promotes Ume6 degradation. Here, we resolve this controversy. First, we identify the set of genes that are directly regulated by Ume6, including UME6 itself. While Ume6 protein levels increase in response to Ime1, Ume6 degradation occurs much later in meiosis. Importantly, we found that depletion of Ume6 shortly before meiotic entry is detrimental to EMG activation and gamete formation, whereas tethering of Ume6 to a heterologous activation domain is sufficient to trigger EMG expression and produce viable gametes in the absence of Ime1. We conclude that Ime1 and Ume6 form an activator complex. While Ume6 is indispensable for EMG expression, Ime1 primarily serves as a transactivator for Ume6.