Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α

Summary: Transcription is a highly regulated sequence of stochastic processes utilizing many regulators, including nuclear receptors (NR) that respond to stimuli. Endocrine disrupting chemicals (EDCs) in the environment can compete with natural ligands for nuclear receptors to alter transcription. A...

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Autores principales:	Michael J. Bolt, Pankaj Singh, Caroline E. Obkirchner, Reid T. Powell, Maureen G. Mancini, Adam T. Szafran, Fabio Stossi, Michael A. Mancini
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biological sciences Cell biology Biophysical Chemistry Science Q
Acceso en línea:	https://doaj.org/article/45c83f8c8620468ca475b94663c889a3
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spelling	oai:doaj.org-article:45c83f8c8620468ca475b94663c889a32021-11-20T05:08:33ZEndocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α2589-004210.1016/j.isci.2021.103227https://doaj.org/article/45c83f8c8620468ca475b94663c889a32021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221011950https://doaj.org/toc/2589-0042Summary: Transcription is a highly regulated sequence of stochastic processes utilizing many regulators, including nuclear receptors (NR) that respond to stimuli. Endocrine disrupting chemicals (EDCs) in the environment can compete with natural ligands for nuclear receptors to alter transcription. As nuclear dynamics can be tightly linked to transcription, it is important to determine how EDCs affect NR mobility. We use an EPA-assembled set of 45 estrogen receptor-α (ERα) ligands and EDCs in our engineered PRL-Array model to characterize their effect upon transcription using fluorescence in situ hybridization and fluorescence recovery after photobleaching (FRAP). We identified 36 compounds that target ERα-GFP to a transcriptionally active, visible locus. Using a novel method for multi-region FRAP analysis we find a strong negative correlation between ERα mobility and inverse agonists. Our findings indicate that ERα mobility is not solely tied to transcription but affected highly by the chemical class binding the receptor.Michael J. BoltPankaj SinghCaroline E. ObkirchnerReid T. PowellMaureen G. ManciniAdam T. SzafranFabio StossiMichael A. ManciniElsevierarticleBiological sciencesCell biologyBiophysical ChemistryScienceQENiScience, Vol 24, Iss 11, Pp 103227- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biological sciences Cell biology Biophysical Chemistry Science Q
spellingShingle	Biological sciences Cell biology Biophysical Chemistry Science Q Michael J. Bolt Pankaj Singh Caroline E. Obkirchner Reid T. Powell Maureen G. Mancini Adam T. Szafran Fabio Stossi Michael A. Mancini Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
description	Summary: Transcription is a highly regulated sequence of stochastic processes utilizing many regulators, including nuclear receptors (NR) that respond to stimuli. Endocrine disrupting chemicals (EDCs) in the environment can compete with natural ligands for nuclear receptors to alter transcription. As nuclear dynamics can be tightly linked to transcription, it is important to determine how EDCs affect NR mobility. We use an EPA-assembled set of 45 estrogen receptor-α (ERα) ligands and EDCs in our engineered PRL-Array model to characterize their effect upon transcription using fluorescence in situ hybridization and fluorescence recovery after photobleaching (FRAP). We identified 36 compounds that target ERα-GFP to a transcriptionally active, visible locus. Using a novel method for multi-region FRAP analysis we find a strong negative correlation between ERα mobility and inverse agonists. Our findings indicate that ERα mobility is not solely tied to transcription but affected highly by the chemical class binding the receptor.
format	article
author	Michael J. Bolt Pankaj Singh Caroline E. Obkirchner Reid T. Powell Maureen G. Mancini Adam T. Szafran Fabio Stossi Michael A. Mancini
author_facet	Michael J. Bolt Pankaj Singh Caroline E. Obkirchner Reid T. Powell Maureen G. Mancini Adam T. Szafran Fabio Stossi Michael A. Mancini
author_sort	Michael J. Bolt
title	Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
title_short	Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
title_full	Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
title_fullStr	Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
title_full_unstemmed	Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
title_sort	endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/45c83f8c8620468ca475b94663c889a3
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Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α

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