FUNCTIONAL ANTAGONISM BETWEEN RNA-POLYMERASE-II HOLOENZYME AND GLOBALNEGATIVE REGULATOR NC2 IN-VIVO

Activation of eukaryotic class II gene expression involves the formati on of a transcription initiation complex that includes RNA polymerase II, general transcription factors, and SRB components of the holoenzym e, Negative regulators of transcription have been described, but it is not clear whether any are general repressors of class II genes in viv o. We reasoned that defects in truly global negative regulators should compensate for deficiencies in SRB4 because SRB4 plays a positive rol e in holoenzyme function, Genetic experiments reveal that this is inde ed the case: a defect in the yeast homologue of the human negative reg ulator NC2 (Dr1.DRAP1) suppresses a mutation in SRB4. Global defects i n mRNA synthesis caused by the defective yeast holoenzyme are alleviat ed by the NC2 suppressing mutation in vivo, indicating that yeast NC2 is a global negative regulator of class II transcription, These result s imply that relief from repression at class II promoters is a general feature of gene activation in vivo.