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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Nature Portfolio
2017
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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) |
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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 |
work_keys_str_mv |
AT martinstortz mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT diegompresman mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT lucianabruno mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT paoloannibale mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT mariavdansey mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT gerardoburton mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT enricogratton mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT adalipecci mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape AT valerialevi mappingthedynamicsoftheglucocorticoidreceptorwithinthenuclearlandscape |
_version_ |
1718388679404158976 |