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Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator

In mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA–mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary...

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Autores principales: Gómez Acuña, Luciana I., Nazer, Ezequiel, Rodríguez-Seguí, Santiago A., Pozzi, Berta, Buggiano, Valeria, Marasco, Luciano E., Agirre, Eneritz, He, Cody, Alló, Mariano, Kornblihtt, Alberto R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480116/
https://www.ncbi.nlm.nih.gov/pubmed/32673398
http://dx.doi.org/10.1083/jcb.201908097
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author Gómez Acuña, Luciana I.
Nazer, Ezequiel
Rodríguez-Seguí, Santiago A.
Pozzi, Berta
Buggiano, Valeria
Marasco, Luciano E.
Agirre, Eneritz
He, Cody
Alló, Mariano
Kornblihtt, Alberto R.
author_facet Gómez Acuña, Luciana I.
Nazer, Ezequiel
Rodríguez-Seguí, Santiago A.
Pozzi, Berta
Buggiano, Valeria
Marasco, Luciano E.
Agirre, Eneritz
He, Cody
Alló, Mariano
Kornblihtt, Alberto R.
author_sort Gómez Acuña, Luciana I.
collection PubMed
description In mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA–mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary gland cells, AGO1 associates with transcriptional enhancers of estrogen receptor α (ERα) and that this association is up-regulated by treating the cells with estrogen (E2), displaying a positive correlation with the activation of these enhancers. Moreover, we show that AGO1 interacts with ERα and that this interaction is also increased by E2 treatment, but occurs in the absence of RNA. We show that AGO1 acts positively as a coactivator in estradiol-triggered transcription regulation by promoting ERα binding to its enhancers. Consistently, AGO1 depletion decreases long-range contacts between ERα enhancers and their target promoters. Our results point to a role of AGO1 in transcriptional regulation in human cells that is independent from small RNA binding.
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spelling pubmed-74801162021-03-07 Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator Gómez Acuña, Luciana I. Nazer, Ezequiel Rodríguez-Seguí, Santiago A. Pozzi, Berta Buggiano, Valeria Marasco, Luciano E. Agirre, Eneritz He, Cody Alló, Mariano Kornblihtt, Alberto R. J Cell Biol Report In mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA–mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary gland cells, AGO1 associates with transcriptional enhancers of estrogen receptor α (ERα) and that this association is up-regulated by treating the cells with estrogen (E2), displaying a positive correlation with the activation of these enhancers. Moreover, we show that AGO1 interacts with ERα and that this interaction is also increased by E2 treatment, but occurs in the absence of RNA. We show that AGO1 acts positively as a coactivator in estradiol-triggered transcription regulation by promoting ERα binding to its enhancers. Consistently, AGO1 depletion decreases long-range contacts between ERα enhancers and their target promoters. Our results point to a role of AGO1 in transcriptional regulation in human cells that is independent from small RNA binding. Rockefeller University Press 2020-07-16 /pmc/articles/PMC7480116/ /pubmed/32673398 http://dx.doi.org/10.1083/jcb.201908097 Text en © 2020 Gomez Acuna et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Report
Gómez Acuña, Luciana I.
Nazer, Ezequiel
Rodríguez-Seguí, Santiago A.
Pozzi, Berta
Buggiano, Valeria
Marasco, Luciano E.
Agirre, Eneritz
He, Cody
Alló, Mariano
Kornblihtt, Alberto R.
Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
title Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
title_full Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
title_fullStr Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
title_full_unstemmed Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
title_short Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator
title_sort nuclear role for human argonaute-1 as an estrogen-dependent transcription coactivator
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480116/
https://www.ncbi.nlm.nih.gov/pubmed/32673398
http://dx.doi.org/10.1083/jcb.201908097
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