GENETIC INTERACTIONS BETWEEN SIN3 MUTATIONS AND THE SACCHAROMYCES-CEREVISIAE TRANSCRIPTIONAL ACTIVATORS ENCODED BY MCM1, STE12, AND SWI1

SIN3 was first identified by a mutation which suppresses the effects o f an swi5 mutation on expression of the HO gene in Saccharomyces cerev isiae. We now show that a sin3 mutation also partially suppresses the effects of swi1 on HO transcription, and partially suppresses the grow th defect and inositol requirement observed in swi1 mutants. This sugg ests that SIN3 and SWI1 may play opposite regulatory roles in controll ing expression of many yeast genes. Yeast SIN3 has been shown to funct ion as a negative transcriptional regulator of a number of yeast genes . However, expression of the yeast STE6 gene is reduced in a sin3 muta nt strain. This suggests that SIN3 functions as a positive regulator f or STE6 transcription, although this apparent activation function coul d be indirect. In order to understand how SIN3 functions in STE6 regul ation, we have performed a genetic analysis. It has been previously de monstrated that MCM1 and STE12 are transcriptional activators of a-spe cific genes such as STE6, and we now show that SWI1 is also required f or STE6 expression. Our data suggest that STE12 and SWI1 function in d ifferent pathways of activation, and that STE12 is epistatic to SIN3 a nd SWI1. We show that the activities of the Mcm1p and Ste12p activator s are modestly reduced in a sin3 mutant strain, and that phosphorylati on of the Ste12p activator is decreased in a sin3 mutant. Thus, it is possible that the decreased transcription of STE6 in sin3 mutants is d ue to the combined effect of the diminished activities of Mcm1p and St e12p.