Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape

Abstract The distribution of the transcription machinery among different sub-nuclear domains raises the question on how the architecture of the nucleus modulates the transcriptional response. Here, we used fluorescence fluctuation analyses to quantitatively explore the organization of the glucocorti...

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Autores principales: Martin Stortz, Diego M. Presman, Luciana Bruno, Paolo Annibale, Maria V. Dansey, Gerardo Burton, Enrico Gratton, Adali Pecci, Valeria Levi
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/ef356766e870405287f98d124f438e45
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spelling oai:doaj.org-article:ef356766e870405287f98d124f438e452021-12-02T15:05:55ZMapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape10.1038/s41598-017-06676-02045-2322https://doaj.org/article/ef356766e870405287f98d124f438e452017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06676-0https://doaj.org/toc/2045-2322Abstract The distribution of the transcription machinery among different sub-nuclear domains raises the question on how the architecture of the nucleus modulates the transcriptional response. Here, we used fluorescence fluctuation analyses to quantitatively explore the organization of the glucocorticoid receptor (GR) in the interphase nucleus of living cells. We found that this ligand-activated transcription factor diffuses within the nucleus and dynamically interacts with bodies enriched in the coregulator NCoA-2, DNA-dependent foci and chromatin targets. The distribution of the receptor among the nuclear compartments depends on NCoA-2 and the conformation of the receptor as assessed with synthetic ligands and GR mutants with impaired transcriptional abilities. Our results suggest that the partition of the receptor in different nuclear reservoirs ultimately regulates the concentration of receptor available for the interaction with specific targets, and thus has an impact on transcription regulation.Martin StortzDiego M. PresmanLuciana BrunoPaolo AnnibaleMaria V. DanseyGerardo BurtonEnrico GrattonAdali PecciValeria LeviNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Martin Stortz
Diego M. Presman
Luciana Bruno
Paolo Annibale
Maria V. Dansey
Gerardo Burton
Enrico Gratton
Adali Pecci
Valeria Levi
Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape
description Abstract The distribution of the transcription machinery among different sub-nuclear domains raises the question on how the architecture of the nucleus modulates the transcriptional response. Here, we used fluorescence fluctuation analyses to quantitatively explore the organization of the glucocorticoid receptor (GR) in the interphase nucleus of living cells. We found that this ligand-activated transcription factor diffuses within the nucleus and dynamically interacts with bodies enriched in the coregulator NCoA-2, DNA-dependent foci and chromatin targets. The distribution of the receptor among the nuclear compartments depends on NCoA-2 and the conformation of the receptor as assessed with synthetic ligands and GR mutants with impaired transcriptional abilities. Our results suggest that the partition of the receptor in different nuclear reservoirs ultimately regulates the concentration of receptor available for the interaction with specific targets, and thus has an impact on transcription regulation.
format article
author Martin Stortz
Diego M. Presman
Luciana Bruno
Paolo Annibale
Maria V. Dansey
Gerardo Burton
Enrico Gratton
Adali Pecci
Valeria Levi
author_facet Martin Stortz
Diego M. Presman
Luciana Bruno
Paolo Annibale
Maria V. Dansey
Gerardo Burton
Enrico Gratton
Adali Pecci
Valeria Levi
author_sort Martin Stortz
title Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape
title_short Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape
title_full Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape
title_fullStr Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape
title_full_unstemmed Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape
title_sort mapping the dynamics of the glucocorticoid receptor within the nuclear landscape
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/ef356766e870405287f98d124f438e45
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