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Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling

Forkhead box O (FOXO) transcription factors are key players in diverse cellular processes affecting tumorigenesis, stem cell maintenance and lifespan. To gain insight into the mechanisms of FOXO-regulated target gene expression, we studied genome-wide effects of FOXO3 activation. Profiling RNA polym...

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Autores principales: Eijkelenboom, Astrid, Mokry, Michal, de Wit, Elzo, Smits, Lydia M, Polderman, Paulien E, van Triest, Miranda H, van Boxtel, Ruben, Schulze, Almut, de Laat, Wouter, Cuppen, Edwin, Burgering, Boudewijn M T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564262/
https://www.ncbi.nlm.nih.gov/pubmed/23340844
http://dx.doi.org/10.1038/msb.2012.74
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author Eijkelenboom, Astrid
Mokry, Michal
de Wit, Elzo
Smits, Lydia M
Polderman, Paulien E
van Triest, Miranda H
van Boxtel, Ruben
Schulze, Almut
de Laat, Wouter
Cuppen, Edwin
Burgering, Boudewijn M T
author_facet Eijkelenboom, Astrid
Mokry, Michal
de Wit, Elzo
Smits, Lydia M
Polderman, Paulien E
van Triest, Miranda H
van Boxtel, Ruben
Schulze, Almut
de Laat, Wouter
Cuppen, Edwin
Burgering, Boudewijn M T
author_sort Eijkelenboom, Astrid
collection PubMed
description Forkhead box O (FOXO) transcription factors are key players in diverse cellular processes affecting tumorigenesis, stem cell maintenance and lifespan. To gain insight into the mechanisms of FOXO-regulated target gene expression, we studied genome-wide effects of FOXO3 activation. Profiling RNA polymerase II changes shows that FOXO3 regulates gene expression through transcription initiation. Correlative analysis of FOXO3 and RNA polymerase II ChIP-seq profiles demonstrates FOXO3 to act as a transcriptional activator. Furthermore, this analysis reveals a significant part of FOXO3 gene regulation proceeds through enhancer regions. FOXO3 binds to pre-existing enhancers and further activates these enhancers as shown by changes in histone acetylation and RNA polymerase II recruitment. In addition, FOXO3-mediated enhancer activation correlates with regulation of adjacent genes and pre-existence of chromatin loops between FOXO3 bound enhancers and target genes. Combined, our data elucidate how FOXOs regulate gene transcription and provide insight into mechanisms by which FOXOs can induce different gene expression programs depending on chromatin architecture.
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spelling pubmed-35642622013-02-05 Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling Eijkelenboom, Astrid Mokry, Michal de Wit, Elzo Smits, Lydia M Polderman, Paulien E van Triest, Miranda H van Boxtel, Ruben Schulze, Almut de Laat, Wouter Cuppen, Edwin Burgering, Boudewijn M T Mol Syst Biol Article Forkhead box O (FOXO) transcription factors are key players in diverse cellular processes affecting tumorigenesis, stem cell maintenance and lifespan. To gain insight into the mechanisms of FOXO-regulated target gene expression, we studied genome-wide effects of FOXO3 activation. Profiling RNA polymerase II changes shows that FOXO3 regulates gene expression through transcription initiation. Correlative analysis of FOXO3 and RNA polymerase II ChIP-seq profiles demonstrates FOXO3 to act as a transcriptional activator. Furthermore, this analysis reveals a significant part of FOXO3 gene regulation proceeds through enhancer regions. FOXO3 binds to pre-existing enhancers and further activates these enhancers as shown by changes in histone acetylation and RNA polymerase II recruitment. In addition, FOXO3-mediated enhancer activation correlates with regulation of adjacent genes and pre-existence of chromatin loops between FOXO3 bound enhancers and target genes. Combined, our data elucidate how FOXOs regulate gene transcription and provide insight into mechanisms by which FOXOs can induce different gene expression programs depending on chromatin architecture. European Molecular Biology Organization 2013-01-22 /pmc/articles/PMC3564262/ /pubmed/23340844 http://dx.doi.org/10.1038/msb.2012.74 Text en Copyright © 2013, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-sa/3.0/This article is licensed under a Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License.
spellingShingle Article
Eijkelenboom, Astrid
Mokry, Michal
de Wit, Elzo
Smits, Lydia M
Polderman, Paulien E
van Triest, Miranda H
van Boxtel, Ruben
Schulze, Almut
de Laat, Wouter
Cuppen, Edwin
Burgering, Boudewijn M T
Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
title Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
title_full Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
title_fullStr Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
title_full_unstemmed Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
title_short Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
title_sort genome-wide analysis of foxo3 mediated transcription regulation through rna polymerase ii profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564262/
https://www.ncbi.nlm.nih.gov/pubmed/23340844
http://dx.doi.org/10.1038/msb.2012.74
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