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ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization

Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of mTOR to modulate rRNA levels. ING1 represses rDNA...

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Autores principales: Rajarajacholan, Uma Karthika, Thalappilly, Subhash, Riabowol, Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389678/
https://www.ncbi.nlm.nih.gov/pubmed/27903908
http://dx.doi.org/10.1093/nar/gkw1161
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author Rajarajacholan, Uma Karthika
Thalappilly, Subhash
Riabowol, Karl
author_facet Rajarajacholan, Uma Karthika
Thalappilly, Subhash
Riabowol, Karl
author_sort Rajarajacholan, Uma Karthika
collection PubMed
description Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of mTOR to modulate rRNA levels. ING1 represses rDNA transcription by recruiting HDAC1 to rDNA loci, increasing its association with the NoRC complex and deacetylating the histone H3K9 and H3K27 marks of active transcription. Loss of ING1 enhances nucleolar localization of phospho-mTOR and its association with Raptor and GβL, even during rapamycin treatment. ING1 inhibits rDNA transcription by inhibiting UBF activity and its interaction with mTOR. Regulation of rDNA heterochromatin and rRNA synthesis by ING1 is also apparent during normal cell growth and during cell stress. Moreover, this function was also important during PMA induced differentiation of THP1 cells, since knocking down ING1 affected the process by inhibiting rRNA transcriptional repression. These observations show that ING1 regulates the nucleolar epigenome and rDNA transcription suggesting that regulation of protein synthesis might serve as the basis for ING1 function as a type II tumor suppressor.
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spelling pubmed-53896782017-04-24 ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization Rajarajacholan, Uma Karthika Thalappilly, Subhash Riabowol, Karl Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of mTOR to modulate rRNA levels. ING1 represses rDNA transcription by recruiting HDAC1 to rDNA loci, increasing its association with the NoRC complex and deacetylating the histone H3K9 and H3K27 marks of active transcription. Loss of ING1 enhances nucleolar localization of phospho-mTOR and its association with Raptor and GβL, even during rapamycin treatment. ING1 inhibits rDNA transcription by inhibiting UBF activity and its interaction with mTOR. Regulation of rDNA heterochromatin and rRNA synthesis by ING1 is also apparent during normal cell growth and during cell stress. Moreover, this function was also important during PMA induced differentiation of THP1 cells, since knocking down ING1 affected the process by inhibiting rRNA transcriptional repression. These observations show that ING1 regulates the nucleolar epigenome and rDNA transcription suggesting that regulation of protein synthesis might serve as the basis for ING1 function as a type II tumor suppressor. Oxford University Press 2017-02-28 2016-11-28 /pmc/articles/PMC5389678/ /pubmed/27903908 http://dx.doi.org/10.1093/nar/gkw1161 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Rajarajacholan, Uma Karthika
Thalappilly, Subhash
Riabowol, Karl
ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
title ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
title_full ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
title_fullStr ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
title_full_unstemmed ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
title_short ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
title_sort ing1 regulates rrna levels by altering nucleolar chromatin structure and mtor localization
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389678/
https://www.ncbi.nlm.nih.gov/pubmed/27903908
http://dx.doi.org/10.1093/nar/gkw1161
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