A specialized nucleosome modulates transcription factor access to a C-glabrata metal responsive promoter

The ability of DNA binding transcription factors to access cis-acting promoter elements is critical for transcriptional responses. We demonstrate that rapid transcriptional autoactivation by the Amt1 Cu metalloregulatory transcription factor from the opportunistic pathogenic yeast Candida glabrata is dependent on rapid metal-induced DNA binding to a single metal response element (MRE). In vivo footprinting and chromatin-mapping experiments demonstrate that the MRE and a homopolymeric (dA . dT) element adjacent to the MRE are packaged into a positioned nucleosome that exhibits homopolymeric (dA . dT)-dependent localized distortion. This distortion is critical for rapid Amt1 binding to the MRE, for Cu-dependent AMT1 gene transcription, and for C. glabrata cells to mount a rapid transcriptional response to Cu for normal metal detoxification. The AMT1 promoter represents a novel class of specialized nucleosomal structures that links rapid transcriptional responses to the biology of metal homeostasis.