eprintid: 1344570 rev_number: 35 eprint_status: archive userid: 608 dir: disk0/01/34/45/70 datestamp: 2012-04-27 18:32:44 lastmod: 2021-10-04 00:11:08 status_changed: 2012-04-27 18:32:44 type: article metadata_visibility: show item_issues_count: 0 creators_name: Vaquerizas, JM creators_name: Suyama, R creators_name: Kind, J creators_name: Miura, K creators_name: Luscombe, NM creators_name: Akhtar, A title: Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome. ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: F99 keywords: Animals, Chromatin, Drosophila Proteins, Drosophila melanogaster, Genome, Insect, Male, Nuclear Matrix-Associated Proteins, Nuclear Pore Complex Proteins, Protein Binding, Transcription, Genetic, X Chromosome note: © 2010 Vaquerizas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC2820533 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. date: 2010-02-12 official_url: http://dx.doi.org/10.1371/journal.pgen.1000846 vfaculties: VFLS oa_status: green language: eng primo: open primo_central: open_green article_type_text: Journal Article, Research Support, Non-U.S. Gov't verified: verified_manual elements_source: PubMed elements_id: 398518 doi: 10.1371/journal.pgen.1000846 lyricists_name: Luscombe, Nicholas lyricists_id: NMLUS17 full_text_status: public publication: PLoS Genetics volume: 6 number: 2 pagerange: e1000846 - event_location: US issn: 1553-7390 citation: Vaquerizas, JM; Suyama, R; Kind, J; Miura, K; Luscombe, NM; Akhtar, A; (2010) Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome. PLoS Genetics , 6 (2) e1000846 -. 10.1371/journal.pgen.1000846 <https://doi.org/10.1371/journal.pgen.1000846>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1344570/1/1344570.pdf