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Dynamic Association of NUP98 with the Human Genome
Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors, histone-modification enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins, well known components that control nucl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585015/ https://www.ncbi.nlm.nih.gov/pubmed/23468646 http://dx.doi.org/10.1371/journal.pgen.1003308 |
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author | Liang, Yun Franks, Tobias M. Marchetto, Maria C. Gage, Fred H. Hetzer, Martin W. |
author_facet | Liang, Yun Franks, Tobias M. Marchetto, Maria C. Gage, Fred H. Hetzer, Martin W. |
author_sort | Liang, Yun |
collection | PubMed |
description | Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors, histone-modification enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins, well known components that control nucleo-cytoplasmic trafficking, have wide-ranging functions in developmental gene regulation that potentially extend beyond their role in nuclear transport. Whether the unexpected role of nuclear pore proteins in transcription regulation, which initially has been described in fungi and flies, also applies to human cells is unknown. Here we show at a genome-wide level that the nuclear pore protein NUP98 associates with developmentally regulated genes active during human embryonic stem cell differentiation. Overexpression of a dominant negative fragment of NUP98 levels decreases expression levels of NUP98-bound genes. In addition, we identify two modes of developmental gene regulation by NUP98 that are differentiated by the spatial localization of NUP98 target genes. Genes in the initial stage of developmental induction can associate with NUP98 that is embedded in the nuclear pores at the nuclear periphery. Alternatively, genes that are highly induced can interact with NUP98 in the nuclear interior, away from the nuclear pores. This work demonstrates for the first time that NUP98 dynamically associates with the human genome during differentiation, revealing a role of a nuclear pore protein in regulating developmental gene expression programs. |
format | Online Article Text |
id | pubmed-3585015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35850152013-03-06 Dynamic Association of NUP98 with the Human Genome Liang, Yun Franks, Tobias M. Marchetto, Maria C. Gage, Fred H. Hetzer, Martin W. PLoS Genet Research Article Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors, histone-modification enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins, well known components that control nucleo-cytoplasmic trafficking, have wide-ranging functions in developmental gene regulation that potentially extend beyond their role in nuclear transport. Whether the unexpected role of nuclear pore proteins in transcription regulation, which initially has been described in fungi and flies, also applies to human cells is unknown. Here we show at a genome-wide level that the nuclear pore protein NUP98 associates with developmentally regulated genes active during human embryonic stem cell differentiation. Overexpression of a dominant negative fragment of NUP98 levels decreases expression levels of NUP98-bound genes. In addition, we identify two modes of developmental gene regulation by NUP98 that are differentiated by the spatial localization of NUP98 target genes. Genes in the initial stage of developmental induction can associate with NUP98 that is embedded in the nuclear pores at the nuclear periphery. Alternatively, genes that are highly induced can interact with NUP98 in the nuclear interior, away from the nuclear pores. This work demonstrates for the first time that NUP98 dynamically associates with the human genome during differentiation, revealing a role of a nuclear pore protein in regulating developmental gene expression programs. Public Library of Science 2013-02-28 /pmc/articles/PMC3585015/ /pubmed/23468646 http://dx.doi.org/10.1371/journal.pgen.1003308 Text en © 2013 Liang 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 Liang, Yun Franks, Tobias M. Marchetto, Maria C. Gage, Fred H. Hetzer, Martin W. Dynamic Association of NUP98 with the Human Genome |
title | Dynamic Association of NUP98 with the Human Genome |
title_full | Dynamic Association of NUP98 with the Human Genome |
title_fullStr | Dynamic Association of NUP98 with the Human Genome |
title_full_unstemmed | Dynamic Association of NUP98 with the Human Genome |
title_short | Dynamic Association of NUP98 with the Human Genome |
title_sort | dynamic association of nup98 with the human genome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585015/ https://www.ncbi.nlm.nih.gov/pubmed/23468646 http://dx.doi.org/10.1371/journal.pgen.1003308 |
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