Nuclear Pore Proteins Nup153 and Megator Define Transcriptionally Active Regions in the Drosophila Genome 英文参考文献.docVIP
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Nuclear Pore Proteins Nup153 and Megator Define Transcriptionally Active Regions in the Drosophila Genome 英文参考文献
NuclearPoreProteinsNup153andMegatorDefine
TranscriptionallyActiveRegionsintheDrosophila
Genome
JuanM.Vaquerizas1.,RitsukoSuyama2.,JopKind2.,KotaMiura3,NicholasM.Luscombe1,2*,Asifa
Akhtar2,4
*
1European Bioinformatics Institute, Cambridge, United Kingdom, 2Genome Biology Unit, European Molecular Biology Laboratory,Heidelberg, Germany, 3Centrefor
Molecular and Cellular Imaging, European Molecular Biology Laboratory, Heidelberg, Germany, 4Laboratory of Chromatin Regulation, Max Planck Institute of
Immunobiology,Freiburg,Germany
Abstract
Transcriptionalregulationisoneofthemostimportantprocessesformodulatinggeneexpression.Thoughmuchofthis
controlisattributedtotranscriptionfactors,histones,andassociatedenzymes,itisincreasinglyapparentthatthespatial
organizationofchromosomeswithinthenucleushasaprofoundeffectontranscriptionalactivity.Studiesinyeastindicate
that the nuclear pore complex might promote transcription by recruiting chromatin to the nuclear periphery. In higher
eukaryotes,however,itisnotknownwhethersuchregulationhasglobalsignificance.Hereweestablishnucleoporinsasa
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
continuousdomainsextending10kbto500kb.TheseNucleoporin-AssociatedRegions(NARs)aredominatedbymarkers
foractivetranscription,includinghighRNApolymeraseIIoccupancyandhistoneH4K16acetylation.RNAi–mediatedknock-
downofNup153alterstheexpressionof,5,700genes,withapronounceddown-regulatoryeffectwithinNARs.Wefind
that nucleoporins play a central role in coordinating dosage compensation—an organism-wide process involving the
doublingofexpressionofthemaleXchromosome.NARsareenrichedonthemaleXchromosomeandoccupy75%ofthis
chromosome. Furthermore, Nup153-depletion abolishes the normal function of the male-specific dosage compensation
complex.Finally,byextensive3Dimaging,wedemonstratethatNARscontri
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