title: Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.
abstract: NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx)) has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions.
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kwon
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Valentina
authors.initials: V
authors.lastname: Grisan
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Boyun
authors.initials: B
authors.lastname: Jang
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Herbert
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Badenhorst
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C107964:CP190 protein, Drosophila; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; C437989:E(bx) protein, Drosophila; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; C509085:TRF2 protein, Drosophila; D035341:Telomeric Repeat Binding Protein 2; D014157:Transcription Factors