Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1782258304265748480 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3564262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | European Molecular Biology Organization |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT eijkelenboomastrid genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT mokrymichal genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT dewitelzo genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT smitslydiam genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT poldermanpauliene genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT vantriestmirandah genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT vanboxtelruben genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT schulzealmut genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT delaatwouter genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT cuppenedwin genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling AT burgeringboudewijnmt genomewideanalysisoffoxo3mediatedtranscriptionregulationthroughrnapolymeraseiiprofiling |