Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2

BACKGROUND: The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However,...

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Autores: Marin-Bejar, Oskar, Marchese, Francesco P., Athie, Alejandro, Sanchez, Yolanda, Gonzalez, Jovanna, Segura, Victor, Huang, Lulu, Moreno, Isabel, Navarro Ponz, Alfons, Monzó Planella, Mariano, Garcia-Foncillas, Jesús, Rinn, John L., Guo, Shuling, Huarte, Maite
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/55243
Acceso en línea:https://hdl.handle.net/2445/55243
Access Level:acceso abierto
Palabra clave:Transcripció genètica
Regulació genètica
RNA
Genetic transcription
Genetic regulation
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spelling Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2Marin-Bejar, OskarMarchese, Francesco P.Athie, AlejandroSanchez, YolandaGonzalez, JovannaSegura, VictorHuang, LuluMoreno, IsabelNavarro Ponz, AlfonsMonzó Planella, MarianoGarcia-Foncillas, JesúsRinn, John L.Guo, ShulingHuarte, MaiteTranscripció genèticaRegulació genèticaRNAGenetic transcriptionGenetic regulationRNABACKGROUND: The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs play in this pathway. RESULTS: Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified Pint human ortholog (PINT), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor. CONCLUSIONS: Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate lincRNA.BioMed Central2014201420132014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/55243Articles publicats en revistes (Fonaments Clínics)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1186/gb-2013-14-9-r104Genome Biology, 2013, vol. 14, num. 9, p. R104http://dx.doi.org/10.1186/gb-2013-14-9-r104info:eu-repo/grantAgreement/EC/FP7/281877cc-by-nc (c) Marin-Bejar, O. et al., 2013http://creativecommons.org/licenses/by-nc/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/552432026-05-29T05:05:01Z
dc.title.none.fl_str_mv Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
title Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
spellingShingle Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
Marin-Bejar, Oskar
Transcripció genètica
Regulació genètica
RNA
Genetic transcription
Genetic regulation
RNA
title_short Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
title_full Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
title_fullStr Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
title_full_unstemmed Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
title_sort Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
dc.creator.none.fl_str_mv Marin-Bejar, Oskar
Marchese, Francesco P.
Athie, Alejandro
Sanchez, Yolanda
Gonzalez, Jovanna
Segura, Victor
Huang, Lulu
Moreno, Isabel
Navarro Ponz, Alfons
Monzó Planella, Mariano
Garcia-Foncillas, Jesús
Rinn, John L.
Guo, Shuling
Huarte, Maite
author Marin-Bejar, Oskar
author_facet Marin-Bejar, Oskar
Marchese, Francesco P.
Athie, Alejandro
Sanchez, Yolanda
Gonzalez, Jovanna
Segura, Victor
Huang, Lulu
Moreno, Isabel
Navarro Ponz, Alfons
Monzó Planella, Mariano
Garcia-Foncillas, Jesús
Rinn, John L.
Guo, Shuling
Huarte, Maite
author_role author
author2 Marchese, Francesco P.
Athie, Alejandro
Sanchez, Yolanda
Gonzalez, Jovanna
Segura, Victor
Huang, Lulu
Moreno, Isabel
Navarro Ponz, Alfons
Monzó Planella, Mariano
Garcia-Foncillas, Jesús
Rinn, John L.
Guo, Shuling
Huarte, Maite
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Transcripció genètica
Regulació genètica
RNA
Genetic transcription
Genetic regulation
RNA
topic Transcripció genètica
Regulació genètica
RNA
Genetic transcription
Genetic regulation
RNA
description BACKGROUND: The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs play in this pathway. RESULTS: Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified Pint human ortholog (PINT), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor. CONCLUSIONS: Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate lincRNA.
publishDate 2013
dc.date.none.fl_str_mv 2013
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/55243
url https://hdl.handle.net/2445/55243
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1186/gb-2013-14-9-r104
Genome Biology, 2013, vol. 14, num. 9, p. R104
http://dx.doi.org/10.1186/gb-2013-14-9-r104
info:eu-repo/grantAgreement/EC/FP7/281877
dc.rights.none.fl_str_mv cc-by-nc (c) Marin-Bejar, O. et al., 2013
http://creativecommons.org/licenses/by-nc/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc (c) Marin-Bejar, O. et al., 2013
http://creativecommons.org/licenses/by-nc/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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