title: Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome.
abstract: Transcriptional regulation is one of the most important processes for modulating gene expression. Though much of this control is attributed to transcription factors, histones, and associated enzymes, it is increasingly apparent that the spatial organization of chromosomes within the nucleus has a profound effect on transcriptional activity. Studies in yeast indicate that the nuclear pore complex might promote transcription by recruiting chromatin to the nuclear periphery. In higher eukaryotes, however, it is not known whether such regulation has global significance. Here we establish nucleoporins as a major class of global regulators for gene expression in Drosophila melanogaster. Using chromatin-immunoprecipitation combined with microarray hybridisation, we show that Nup153 and Megator (Mtor) bind to 25% of the genome in continuous domains extending 10 kb to 500 kb. These Nucleoporin-Associated Regions (NARs) are dominated by markers for active transcription, including high RNA polymerase II occupancy and histone H4K16 acetylation. RNAi-mediated knock-down of Nup153 alters the expression of approximately 5,700 genes, with a pronounced down-regulatory effect within NARs. We find that nucleoporins play a central role in coordinating dosage compensation-an organism-wide process involving the doubling of expression of the male X chromosome. NARs are enriched on the male X chromosome and occupy 75% of this chromosome. Furthermore, Nup153-depletion abolishes the normal function of the male-specific dosage compensation complex. Finally, by extensive 3D imaging, we demonstrate that NARs contribute to gene expression control irrespective of their sub-nuclear localization. Therefore, we suggest that NAR-binding is used for chromosomal organization that enables gene expression control.
authors.affiliation: European Bioinformatics Institute, Cambridge, United Kingdom.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Vaquerizas
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Suyama
authors.forename: Jop
authors.initials: J
authors.lastname: Kind
authors.forename: Kota
authors.initials: K
authors.lastname: Miura
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
authors.forename: Asifa
authors.initials: A
authors.lastname: Akhtar
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D049750:Genome, Insect / Q000235:genetics*; D008297:Male; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D011485:Protein Binding; D014158:Transcription, Genetic; D014960:X Chromosome / Q000378:metabolism
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; C498867:Mtor protein, Drosophila; D034521:Nuclear Matrix-Associated Proteins; D028861:Nuclear Pore Complex Proteins; C523209:Nup153 protein, Drosophila