|Ph.D Student||Shenhar Galit|
|Subject||Transcriptional Regulation of IMEI, the Master Regulator|
of Meiosis in Budding Yeast
|Department||Department of Biology||Supervisor||Professor Emeritus Yona Kassir|
The choice between meiosis and alternative developmental pathways in budding yeast depends on the expression and activity of the transcriptional activator Ime1. The transcription of IME1 is repressed in the presence of glucose, and a low basal level of IME1 RNA is observed with acetate as the sole carbon source. Upon nitrogen depletion a transient induction in the transcription of IME1 is observed in MATa/MATa diploids. An extremely unusual large 5' region, over 2100 bp long, controls the transcription of IME1.
In this study we identified two specific elements in IME1 promoter, IREu and UASru, that are regulated by the carbon source signal. We showed that the glucose signal that determines the activity of IREu element is transmitted to IREu through the Ras/cAMP pathway, and that the MAPK cascade, transmits the glucose signal to UASru. .
We showed that the activity of IREu in acetate media depends on three transcriptional activators Msn2/4 and Ime1 itself. Msn2 and Msn4 bind directly to IREu, probably via its STRE sequence. We also showed that Sok2 mediates the repression activity of IREu in glucose media and that it also binds IREu. Sok2 associates with Msn2 and functions as a general repressor whose availability and activity depends on glucose. The activity of Sok2 as a repressor depends on phosphorylation of T598 by protein kinase A. Relief of repression of Sok2 depends on both the N-terminal domain of Sok2 and Ime1. Over-expression of Sok2 or mild expression of Sok2 deleted for its N-terminal domain led to a decrease in sporulation.
Our results demonstrate that Sok2, a positive regulator of mitosis, functions as a negative regulator of meiosis, whereas Msn2 a negative regulator of mitosis function as a positive regulator of meiosis. We suggest that cells use the same regulator with opposing effects to ensure that meiosis will be an alternative to mitosis.