title: Chromatin remodelers clear nucleosomes from intrinsically unfavorable sites to establish nucleosome-depleted regions at promoters.
abstract: Most promoters in yeast contain a nucleosome-depleted region (NDR), but the mechanisms by which NDRs are established and maintained in vivo are currently unclear. We have examined how genome-wide nucleosome placement is altered in the absence of two distinct types of nucleosome remodeling activity. In mutants of both SNF2, which encodes the ATPase component of the Swi/Snf remodeling complex, and ASF1, which encodes a histone chaperone, distinct sets of gene promoters carry excess nucleosomes in their NDRs relative to wild-type. In snf2 mutants, excess promoter nucleosomes correlate with reduced gene expression. In both mutants, the excess nucleosomes occupy DNA sequences that are energetically less favorable for nucleosome formation, indicating that intrinsic histone-DNA interactions are not sufficient for nucleosome positioning in vivo, and that Snf2 and Asf1 promote thermodynamic equilibration of nucleosomal arrays. Cells lacking SNF2 or ASF1 still accomplish the changes in promoter nucleosome structure associated with large-scale transcriptional reprogramming. However, chromatin reorganization in the mutants is reduced in extent compared to wild-type cells, even though transcriptional changes proceed normally. In summary, active remodeling is required for distributing nucleosomes to energetically favorable positions in vivo and for reorganizing chromatin in response to changes in transcriptional activity.
authors.affiliation: Department of Physics and Astronomy and BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Tolkunov
authors.forename: Karl A
authors.initials: KA
authors.lastname: Zawadzki
authors.forename: Cara
authors.initials: C
authors.lastname: Singer
authors.forename: Nils
authors.initials: N
authors.lastname: Elfving
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Morozov
authors.forename: James R
authors.initials: JR
authors.lastname: Broach
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C499333:SNF2 protein, S cerevisiae