title: Nucleoporin mediated nuclear positioning and silencing of HMR.
abstract: The organization of chromatin domains in the nucleus is an important factor in gene regulation. In eukaryotic nuclei, transcriptionally silenced chromatin clusters at the nuclear periphery while transcriptionally poised chromatin resides in the nuclear interior. Recent studies suggest that nuclear pore proteins (NUPs) recruit loci to nuclear pores to aid in insulation of genes from silencing and during gene activation. We investigated the role of NUPs at a native yeast insulator and show that while NUPs localize to the native tDNA insulator adjacent to the silenced HMR domain, loss of pore proteins does not compromise insulation. Surprisingly we find that NUPs contribute to silencing at HMR and are able to restore silencing to a silencing-defective HMR allele when tethered to the locus. We show that the perinuclear positioning of heterochromatin is important for the NUP-mediated silencing effect and find that loss of NUPs result in decreased localization of HMR to the nuclear periphery. We also show that loss of telomeric tethering pathways does not eliminate NUP localization to HMR, suggesting that NUPs may mediate an independent pathway for HMR association with the nuclear periphery. We propose that localization of NUPs to the tDNA insulator at HMR helps maintain the intranuclear position of the silent locus, which in turn contributes to the fidelity of silencing at HMR.
authors.affiliation: Department of Molecular Cell Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
authors.forename: Giulia J
authors.initials: GJ
authors.lastname: Ruben
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Kirkland
authors.forename: Tracy
authors.initials: T
authors.lastname: MacDonough
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.forename: Rudra N
authors.initials: RN
authors.lastname: Dubey
authors.forename: Marc R
authors.initials: MR
authors.lastname: Gartenberg
authors.forename: Rohinton T
authors.initials: RT
authors.lastname: Kamakaka
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000235:genetics; D004271:DNA, Fungal / Q000378:metabolism; D020868:Gene Silencing; D056426:Genetic Loci / Q000235:genetics*; D006570:Heterochromatin / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016615:Telomere / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D006570:Heterochromatin; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins