title: Remodelers organize cellular chromatin by counteracting intrinsic histone-DNA sequence preferences in a class-specific manner.
abstract: The nucleosome is the fundamental repeating unit of eukaryotic chromatin. Here, we assessed the interplay between DNA sequence and ATP-dependent chromatin-remodeling factors (remodelers) in the nucleosomal organization of a eukaryotic genome. We compared the genome-wide distribution of Drosophila NURD, (P)BAP, INO80, and ISWI, representing the four major remodeler families. Each remodeler has a unique set of genomic targets and generates distinct chromatin signatures. Remodeler loci have characteristic DNA sequence features, predicted to influence nucleosome formation. Strikingly, remodelers counteract DNA sequence-driven nucleosome distribution in two distinct ways. NURD, (P)BAP, and INO80 increase histone density at their target sequences, which intrinsically disfavor positioned nucleosome formation. In contrast, ISWI promotes open chromatin at sites that are propitious for precise nucleosome placement. Remodelers influence nucleosome organization genome-wide, reflecting their high genomic density and the propagation of nucleosome redistribution beyond remodeler binding sites. In transcriptionally silent early embryos, nucleosome organization correlates with intrinsic histone-DNA sequence preferences. Following differential expression of the genome, however, this relationship diminishes and eventually disappears. We conclude that the cellular nucleosome landscape is the result of the balance between DNA sequence-driven nucleosome placement and active nucleosome repositioning by remodelers and the transcription machinery.
authors: Department of Biochemistry and Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Yuri M
authors: YM
authors: Moshkin
authors: Gillian E
authors: GE
authors: Chalkley
authors: Tsung Wai
authors: TW
authors: Kan
authors: B Ashok
authors: BA
authors: Reddy
authors: Zeliha
authors: Z
authors: Ozgur
authors: Wilfred F J
authors: WF
authors: van Ijcken
authors: Dick H W
authors: DH
authors: Dekkers
authors: Jeroen A
authors: JA
authors: Demmers
authors: Andrew A
authors: AA
authors: Travers
authors: C Peter
authors: CP
authors: Verrijzer
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D016678:Genome; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D006657:Histones; C553462:INO80 protein, Drosophila; C086468:ISWI protein; D009707:Nucleosomes; D014157:Transcription Factors; D004247:DNA; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases