Complex roles of SIN4, RGR1 and ACT3 in yeast transcriptional regulation

SIN4, RGR1 and ACT3 have complex roles in yeast transcriptional regulation. SIN4 and RGR1 are required for both transcriptional activation and repression in vivo. Since sin4 null and rgr1 truncation mutants have similar phenotypes of a strain carrying a histone mutation, it has been proposed that SIN4 and RGR1 affect transcription via chromatin structure. Although the recent discovery that Sin4 and Rgr1 as two subunits of Pol II mediator complex seemingly contradicts this model, the failure to detect any contribution from Sin4 and Rgr1 to Pol II mediator activity in vitro with naked DNA templates suggests that the involvement of chromatin cannot be easily dismissed. Like some histone mutations, a sin4 deletion mutation (sin4Delta) suppresses histidine auxotrophy caused by a transposon insertion mutation in HIS4 (his-912delta). A quantitative analysis of the suppression by sin4Delta revealed that about 10% of the cells are histidine prototrophic and the rest are histidine auxotrophic. A hypothesis of epigenetic control of gene expression has been proposed to explain the phenotype that cells of the same genotype show two phenotypes. Although it is technically difficult to demonstrate that the sin4/Delta mutation suppresses his-912delta in a variegated manner, mutations that suppress his-912delta in a variegated fashion have been isolated. The variegation observed in this study seems to be distinctive and novel, since it shares no modifiers with the position effect variegation in yeast. ACT3, which encodes a nucleus-localized actin-like protein, has been found being a player in this new type of variegation. In act3 mutants, there are two transcriptional states of his-912delta, and these two transcriptional states dictate two phenotypical states. Possible relationships among nuclear skeleton, chromatin structure and transcriptional regulation are discussed.