title: The Candida glabrata Amt1 copper-sensing transcription factor requires Swi/Snf and Gcn5 at a critical step in copper detoxification.
abstract: The yeast Candida glabrata rapidly autoactivates transcription of the AMT1 gene in response to potentially toxic copper levels through the copper-inducible binding of the Amt1 transcription factor to a metal response element (MRE) within a positioned nucleosome. Our previous studies have characterized the role of a 16 bp homopolymeric dA:dT DNA structural element in facilitating rapid Amt1 access to the AMT1 promoter nucleosomal MRE. In this study, we have used the genetically more facile yeast Saccharomyces cerevisiae to identify additional cellular factors that are important for promoting rapid autoactivation of the AMT1 gene in response to toxic copper levels. We demonstrate that the Swi/Snf nucleosome remodelling complex and the histone acetyltransferase Gcn5 are both essential for AMT1 gene autoregulation, and that the requirement for these chromatin remodelling factors is target gene specific. Chromatin accessibility measurements performed in vitro and in vivo indicate that part of the absolute requirement for these factors is derived from their involvement in facilitating nucleosomal access to the AMT1 promoter MRE. Additionally, these data implicate the involvement of Swi/Snf and Gcn5 at multiple levels of AMT1 gene autoregulation.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Koch
authors.forename: S
authors.initials: S
authors.lastname: Allard
authors.forename: N
authors.initials: N
authors.lastname: Santoro
authors.forename: J
authors.initials: J
authors.lastname: Côté
authors.forename: D J
authors.initials: DJ
authors.lastname: Thiele
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D001673:Biodegradation, Environmental; D002175:Candida / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D002843:Chromatin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D002352:Carrier Proteins; D002843:Chromatin; D003300:Copper; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D008668:Metallothionein; D009707:Nucleosomes; D011494:Protein Kinases; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C500769:CUP1-1 protein, S cerevisiae; C007121:copper thionein; C089969:snf protein, Drosophila; C069807:AMT1 protein, Candida glabrate; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C110880:histone acetyltransferase type B complex