The relationship among transcriptional activators, nucleosome repositioning activity and transcription machinery at the yeast CUP1 gene was addressed. CUP1 encodes a cysteine-rich, copper-binding metallothionein that protects cells against copper toxicity through its ability to sequester copper. The induction of CUP1 requires the presence of Ace1p and the binding of Ace1p at the CUP1 promoter during activation provides evidence that Ace1p is directly involved in CUP1 induction. Furthermore, transcriptional activation of CUP1 resulted in nucleosome repositioning at the CUP1 promoter and sequences further downstream in the coding region, suggesting a gene-wide chromatin remodeling activity. Such remodeling activity depends on the presence of transcription activator Ace1p. The recruitment of RNA polymerase II also requires the presence of Ace1p. Therefore, these observations provide insight into the molecular mechanism of CUP1 activation. (C) 2012 Elsevier Inc. All rights reserved.