Nuclear Pore Proteins Nup153 and Megator Define Transcriptionally Active Regions in the Drosophila Genome

摘要: Transcriptional regulation is one of the most important processes for modulating gene expression. Though much this control attributed to transcription factors, histones, and associated enzymes, it increasingly apparent that spatial organization chromosomes within nucleus has a profound effect on transcriptional activity. Studies in yeast indicate nuclear pore complex might promote by recruiting chromatin periphery. In higher eukaryotes, however, not known whether such global significance. Here we establish nucleoporins as major class regulators expression Drosophila melanogaster. Using chromatin-immunoprecipitation combined with microarray hybridisation, show Nup153 Megator (Mtor) bind 25% genome continuous domains extending 10 kb 500 kb. These Nucleoporin-Associated Regions (NARs) are dominated markers active transcription, including high RNA polymerase II occupancy histone H4K16 acetylation. RNAi-mediated knock-down alters approximately 5,700 genes, pronounced down-regulatory NARs. We find play central role coordinating dosage compensation-an organism-wide process involving doubling male X chromosome. NARs enriched chromosome occupy 75% Furthermore, Nup153-depletion abolishes normal function male-specific compensation complex. Finally, extensive 3D imaging, demonstrate contribute irrespective their sub-nuclear localization. Therefore, suggest NAR-binding used chromosomal enables control.