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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 principales: Marín-Béjar, Oskar, Marchese, Francesco P, Athie, Alejandro, Sánchez, Yolanda, González, Jovanna, Segura, Victor, Huang, Lulu, Moreno, Isabel, Navarro, Alfons, Monzó, Mariano, García-Foncillas, Jesús, Rinn, John L, Guo, Shuling, Huarte, Maite
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053822/
https://www.ncbi.nlm.nih.gov/pubmed/24070194
http://dx.doi.org/10.1186/gb-2013-14-9-r104
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author Marín-Béjar, Oskar
Marchese, Francesco P
Athie, Alejandro
Sánchez, Yolanda
González, Jovanna
Segura, Victor
Huang, Lulu
Moreno, Isabel
Navarro, Alfons
Monzó, Mariano
García-Foncillas, Jesús
Rinn, John L
Guo, Shuling
Huarte, Maite
author_facet Marín-Béjar, Oskar
Marchese, Francesco P
Athie, Alejandro
Sánchez, Yolanda
González, Jovanna
Segura, Victor
Huang, Lulu
Moreno, Isabel
Navarro, Alfons
Monzó, Mariano
García-Foncillas, Jesús
Rinn, John L
Guo, Shuling
Huarte, Maite
author_sort Marín-Béjar, Oskar
collection PubMed
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.
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spelling pubmed-40538222014-06-12 Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2 Marín-Béjar, Oskar Marchese, Francesco P Athie, Alejandro Sánchez, Yolanda González, Jovanna Segura, Victor Huang, Lulu Moreno, Isabel Navarro, Alfons Monzó, Mariano García-Foncillas, Jesús Rinn, John L Guo, Shuling Huarte, Maite Genome Biol Research 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. BioMed Central 2013 2013-09-26 /pmc/articles/PMC4053822/ /pubmed/24070194 http://dx.doi.org/10.1186/gb-2013-14-9-r104 Text en Copyright © 2013 Marín-Béjar et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Marín-Béjar, Oskar
Marchese, Francesco P
Athie, Alejandro
Sánchez, Yolanda
González, Jovanna
Segura, Victor
Huang, Lulu
Moreno, Isabel
Navarro, Alfons
Monzó, Mariano
García-Foncillas, Jesús
Rinn, John L
Guo, Shuling
Huarte, Maite
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
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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053822/
https://www.ncbi.nlm.nih.gov/pubmed/24070194
http://dx.doi.org/10.1186/gb-2013-14-9-r104
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