 switches between different phenotypes and their underlying states of gene transcription occur as cells respond to intrinsic developmental cues or adapt to changing environmental conditions . 
 post - translational modification of the master regulatory transcription factors that define the initial phenotype is a common strategy to direct such transitions . 
 emerging evidence indicates that the modification of key transcription factors by the small polypeptide ubiquitin plays a central role in many of these transitions1 , 2 . 
 however , the molecular mechanisms by which ubiquitination regulates the switching of promoters between active and inactive states are largely unknown . 
 ubiquitination of the yeast transcriptional repressor 2 is necessary to evoke the transition between mating - types3 , and here , we dissected the impact of this modification on 2 dynamics at its target promoters . 
 the ubiquitination of 2 does not alter dna occupancy by depleting the existing pool of the transcription factor , despite its well - characterized function in directing repressor turnover . 
 rather , 2 ubiquitination plays a direct role in the rapid removal of the repressor from its dna targets . 
 this disassembly of 2 from dna depends on the ubiquitin - selective aaa - atpase cdc48 . 
 our findings expand the functional targets of cdc48 to active transcriptional regulatory complexes in the nucleus , a far broader role than previously anticipated . 
 these data reveal an ubiquitin - dependent extraction pathway for dismantling transcription factor - dna complexes and provide an archetype for the regulation of transcriptional switching events by ubiquitination . 
Supplementary Material