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

The process of gametogenesis is orchestrated by a dynamic program of gene expression, where a vital subset constitutes the early meiotic genes (EMGs). In budding yeast, the transcription factor Ume6 represses EMG expression during mitosis. However, during mitosis to meiosis transition, EMGs are activated in response to the meiotic 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 a coactivator 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 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 function as a coactivator complex. While Ume6 is indispensable for EMG expression, Ime1 primarily serves as a transactivator for Ume6. ### Competing Interest Statement The authors have declared no competing interest.