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The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing
Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the acti...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495395/ https://www.ncbi.nlm.nih.gov/pubmed/26080816 http://dx.doi.org/10.1101/gad.260919.115 |
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author | Jacinto, Filipe V. Benner, Chris Hetzer, Martin W. |
author_facet | Jacinto, Filipe V. Benner, Chris Hetzer, Martin W. |
author_sort | Jacinto, Filipe V. |
collection | PubMed |
description | Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the activation and silencing of developmental genes; however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the derepression of developmental genes and induction of early differentiation. This loss of stem cell identity is not associated with defects in the nuclear import of key pluripotency factors. Rather, Nup153 binds around the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb-repressive complex 1 (PRC1) to a subset of its target loci. Our results demonstrate a chromatin-associated role of Nup153 in maintaining stem cell pluripotency by functioning in mammalian epigenetic gene silencing. |
format | Online Article Text |
id | pubmed-4495395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44953952015-12-15 The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing Jacinto, Filipe V. Benner, Chris Hetzer, Martin W. Genes Dev Research Paper Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the activation and silencing of developmental genes; however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the derepression of developmental genes and induction of early differentiation. This loss of stem cell identity is not associated with defects in the nuclear import of key pluripotency factors. Rather, Nup153 binds around the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb-repressive complex 1 (PRC1) to a subset of its target loci. Our results demonstrate a chromatin-associated role of Nup153 in maintaining stem cell pluripotency by functioning in mammalian epigenetic gene silencing. Cold Spring Harbor Laboratory Press 2015-06-15 /pmc/articles/PMC4495395/ /pubmed/26080816 http://dx.doi.org/10.1101/gad.260919.115 Text en © 2015 Jacinto et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Jacinto, Filipe V. Benner, Chris Hetzer, Martin W. The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing |
title | The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing |
title_full | The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing |
title_fullStr | The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing |
title_full_unstemmed | The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing |
title_short | The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing |
title_sort | nucleoporin nup153 regulates embryonic stem cell pluripotency through gene silencing |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495395/ https://www.ncbi.nlm.nih.gov/pubmed/26080816 http://dx.doi.org/10.1101/gad.260919.115 |
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