title: Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts.
abstract: Nuclear pore complex components (Nups) have been implicated in transcriptional regulation, yet what regulatory steps are controlled by metazoan Nups remains unclear. We identified the presence of multiple Nups at promoters, enhancers, and insulators in the Drosophila genome. In line with this binding, we uncovered a functional role for Nup98 in mediating enhancer-promoter looping at ecdysone-inducible genes. These genes were found to be stably associated with nuclear pores before and after activation. Although changing levels of Nup98 disrupted enhancer-promoter contacts, it did not affect ongoing transcription but instead compromised subsequent transcriptional activation or transcriptional memory. In support of the enhancer-looping role, we found Nup98 to gain and retain physical interactions with architectural proteins upon stimulation with ecdysone. Together, our data identify Nups as a class of architectural proteins for enhancers and supports a model in which animal genomes use the nuclear pore as an organizing scaffold for inducible poised genes.
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Pau
authors.initials: P
authors.lastname: Pascual-Garcia
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Debo
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Aleman
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Talamas
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yemin
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Nha H
authors.initials: NH
authors.lastname: Nguyen
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kyoung J
authors.initials: KJ
authors.lastname: Won
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: capelson@mail.med.upenn.edu.
authors.forename: Maya
authors.initials: M
authors.lastname: Capelson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004440:Ecdysone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D005838:Genotype; D038101:Insulator Elements; D009154:Mutation; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D028861:Nuclear Pore Complex Proteins; C093350:nuclear pore complex protein 98; D004440:Ecdysone
keywords: Nup98; enhancer; genome architecture; looping; nuclear organization; nuclear pore complex; nucleoporin; poised genes; transcription; transcriptional memory