Association of distinct yeast Not2 functional domains with components of Gcn5 histone acetylase and Ccr4 transcriptional regulatory complexes

The NOT genes were originally identified in a yeast genetic screen that sel ected mutations resulting in increased utilization of a non-consensus T-C T ATA element of the HIS3 promoter. Here, we present evidence that the N-term inus of NotZ interacts with components of the Ada/Gcn5 histone acetyltransf erase complex. Loss of this interaction either through abrogation of Not2 N -terminal function or deletion of ada2 or gcn5 results in derepression of t he HIS3 Te element. This suggests that association of Not2,vith the Ada/Gcn 5 histone acetyltransferase complex is involved in regulation of the HIS3 p romoter. Association between the Not and CCR4 transcriptional regulatory co mplexes has also been observed recently. Our phenotypic analyses suggest th at these CCR4-related Not2 functions are mediated by a functionally indepen dent domain of Not2 that includes the highly conserved C-terminus, Chimeric proteins containing the yeast Not2 N-terminus fused to the human C-terminu s function in yeast, suggesting that the Not2 C-terminus represents a disti nct modular domain whose function is conserved between higher and lower euk aryotes.