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.

Multi-signal regulation of the GSK-3β homolog Rim11 governs meiosis entry in yeast

“…Additionally, the strain also carried a construct harbouring an NLS-containing mRuby3 expressed from the IME1 promoter to label nuclear meiotic divisions. As a readout for EMG expression, we used Ume6 itself because Ume6 directly regulates its own promoter and thus, like EMGs, is transcriptionally induced in early meiosis 13 .…”

“…Under nutrient rich conditions Ume6 is a repressor of EMGs, by recruiting the co-repressor and histone deacetylase complex Sin3-Rpd3L 9,[13][14][15] . When diploid cells are starved, Ume6 and Ime1 interact, which drives the transcription of the EMGs 13,14 . The kinase Rim11 and GSK-3β homolog also plays critical role in the activation of EMGs.…”

Control of meiotic entry by dual inhibition of a key mitotic transcription factor

“…In mitotically dividing cells, Ime1 target genes are repressed by Ume6 through its association with the Sin3-Rpd3 histone deacetylase complex ( Kadosh and Struhl, 1997 ; Rundlett et al, 1998 ). However, under nutrient starvation, entry into the meiotic program is initiated by the interaction between Ime1 and Ume6, which together function as a transcriptional activator, culminating in the induction of early meiotic genes ( Bowdish et al, 1995 ; Harris and Ünal, 2023 ). Mitosis to meiosis transition requires dynamic remodeling of the gene regulatory networks to maintain the mutual exclusivity of these programs.…”

In Saccharomyces cerevisiae ρ0 Cells, UME6 Contributes to the Activation of ABC Transporter Genes and Pleiotropic Drug Resistance via RPD3 and PDR3

“…In addition to their roles as transcriptional repressors, Ume6 and Rpd3 play roles as transcriptional activators. The meiosis-specific transcriptional activator Ime1 binds to Ume6 and converts Ume6 from a transcriptional repressor to a transcriptional activator to release EMGs from repression [42]. Rpd3 functions as a transcriptional activator for the anaerobic genes DAN/TIR and osmoresponsive genes [43,44].…”