UC Berkeley

Transcription factors induce dynamic changes in gene expression to drive cellular differentiation. During the mitotic G1/S of budding yeast when the cell irreversibly commits to divide, transcription factors SBF(Swi4-Swi6) and MBF(Mbp1-Swi6) play essential roles by activating the expression of the G1/S transcriptome. While SBF and MBF act in parallel to mediate the mitotic G1/S transition, their regulation and function in meiosis have remained elusive. Here we characterize both the functional impact of SBF activation on meiotic entry and the molecular mechanisms restricting SBF activity in meiosis.

We first elucidated the functional significance of SBF activity restriction in meiosis and found that elevation of Swi4 protein levels was sufficient to activate SBF, resulting in mis-expression of SBF targets in meiosis. Further experimentation led us to discover that untimely SBF activation caused downregulation of early meiotic genes and delayed meiotic entry. Meiotic entry delays were caused by reduction in the function of Ime1, a master transcriptional regulator of meiosis. Among the SBF targets, G1 cyclins were the main driver of meiotic delays. We further found that G1 cyclins blocked the interaction between Ime1 and its cofactor Ume6.

We next investigated how SBF activity is restricted during meiosis and identified two parallel mechanisms: repression of the SBF-specific Swi4 subunit through LUTI-based regulation and inhibition of SBF by Whi5, a homolog of the Rb tumor suppressor. Our study provides insight into the role of SWI4LUTI in establishing the meiotic transcriptional program and demonstrates how the LUTI-based regulation is integrated into a larger regulatory network to ensure timely SBF activity.