TSF1 TO TSF6, REQUIRED FOR SILENCING THE SACCHAROMYCES-CEREVISIAE GALGENES, ARE GLOBAL REGULATORY GENES

The Saccharomyces cerevisiae GAL1 and GAL10 genes are controlled in re sponse to the availability of galactose and glucose by multiple activa ting and repressing proteins bound at adjacent or overlapping sites in UAS(G). Negative control elements in UAS(G), designated GAL operators GALO1 to GALO6, are required to silence basal level transcription of GAL1 and GAL10 when galactose is absent. We isolated and characterized recessive mutations in six nuclear genes, TSF1 to TSF6, that impair s ilencing of GAL1 and GAL10 gene expression. Surprisingly, the results of several experiments suggest that the TSF genes encode global regula tory factors. tsf1 to tsf6 mutations derepressed expression from yeast CYC-GAL hybrid promoters (fused to lacZ) that harbor a variety of ope rator sequences, and caused pleiotropic defects in cell growth, mating , and sporulation. S1 mapping and Northern blot results for tsf3 sugge st that the molecular defect is at the transcriptional level. Mutant p henotypes were additive in certain combinations of tsf double mutants, implying that more than one silencing pathway is involved in TSF1 to TSF6 function. Most significantly, mutations in all six TSF1 to TSF6 g enes activated expression from GAL1 and CYC1 promoters (fused to lacZ) lacking upstream activating sequences. Combined, the simplest interpr etation of these results is that TSF1 to TSF6 encode factors that cont rol the function of the basic RNA polymerase II transcriptional machin ery.