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Nucleoporin Mediated Nuclear Positioning and Silencing of HMR

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 p...

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Autores principales: Ruben, Giulia J., Kirkland, Jacob G., MacDonough, Tracy, Chen, Miao, Dubey, Rudra N., Gartenberg, Marc R., Kamakaka, Rohinton T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139579/
https://www.ncbi.nlm.nih.gov/pubmed/21818277
http://dx.doi.org/10.1371/journal.pone.0021923
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author Ruben, Giulia J.
Kirkland, Jacob G.
MacDonough, Tracy
Chen, Miao
Dubey, Rudra N.
Gartenberg, Marc R.
Kamakaka, Rohinton T.
author_facet Ruben, Giulia J.
Kirkland, Jacob G.
MacDonough, Tracy
Chen, Miao
Dubey, Rudra N.
Gartenberg, Marc R.
Kamakaka, Rohinton T.
author_sort Ruben, Giulia J.
collection PubMed
description 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.
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spelling pubmed-31395792011-08-04 Nucleoporin Mediated Nuclear Positioning and Silencing of HMR Ruben, Giulia J. Kirkland, Jacob G. MacDonough, Tracy Chen, Miao Dubey, Rudra N. Gartenberg, Marc R. Kamakaka, Rohinton T. PLoS One Research Article 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. Public Library of Science 2011-07-19 /pmc/articles/PMC3139579/ /pubmed/21818277 http://dx.doi.org/10.1371/journal.pone.0021923 Text en Ruben et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Ruben, Giulia J.
Kirkland, Jacob G.
MacDonough, Tracy
Chen, Miao
Dubey, Rudra N.
Gartenberg, Marc R.
Kamakaka, Rohinton T.
Nucleoporin Mediated Nuclear Positioning and Silencing of HMR
title Nucleoporin Mediated Nuclear Positioning and Silencing of HMR
title_full Nucleoporin Mediated Nuclear Positioning and Silencing of HMR
title_fullStr Nucleoporin Mediated Nuclear Positioning and Silencing of HMR
title_full_unstemmed Nucleoporin Mediated Nuclear Positioning and Silencing of HMR
title_short Nucleoporin Mediated Nuclear Positioning and Silencing of HMR
title_sort nucleoporin mediated nuclear positioning and silencing of hmr
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139579/
https://www.ncbi.nlm.nih.gov/pubmed/21818277
http://dx.doi.org/10.1371/journal.pone.0021923
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