Hir1 and Ssn6 coregulators function in combination on the Mac1-dependent CTR1 transcription.
Alexandra Voutsina, Kalliopi Gkouskou, Despina Alexandraki
Biology-Yeast Mol. Genetics, FORTH-IMBB and Univ. of Crete, P.O. BOX 1527, Heraklion-Crete, 71110, Greece
Hir1 corepressor of the cell cycle-regulated transcription of core histone genes also involved in heterochromatic gene silencing and the formation of nucleosomes and kinetochores was identified as a Mac1-interacting protein. We report new roles for Hir1 protein on RNA polymerase II promoters independent of cell cycle signals. Mac1, the first yeast DNA-sequence specific transcriptional activator shown to interact with Hir1, regulates genes responsible for copper entrance and utilization and is active under low copper and copper deficiency and inactive under high copper conditions. The least conserved Hir1 C-terminal half associates directly with the DNA binding domain of Mac1. Hir1 is recruited on the promoter of CTR1 gene (encoding for a high affinity copper transporter) quantitatively under induction conditions and in a Mac1-dependent manner. We have also identified a novel physical association of Hir1 with Ssn6 corepressor that is similarly recruited on CTR1 promoter. Hir1 facilitates CTR1 transcriptional activation revealed in the absence of Ssn6. Ssn6 has a dominant repressive effect on the non-induced (low copper) promoter and an inducing effect alternative to that of Hir1 under full induction. Mac1 activation function, positively affected by Hir1 and dually affected by Ssn6, is predominantly mediated by the Snf2 component of the Swi-Snf chromatin remodeling complex (known to interact with Hir1). Additional Mac1-Hir1 partners are currently analyzed.