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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2013-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2012.74 |
| _version_ | 1797280437973811200 |
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| author | Astrid Eijkelenboom Michal Mokry Elzo de Wit Lydia M Smits Paulien E Polderman Miranda H van Triest Ruben van Boxtel Almut Schulze Wouter de Laat Edwin Cuppen Boudewijn M T Burgering |
| author_facet | Astrid Eijkelenboom Michal Mokry Elzo de Wit Lydia M Smits Paulien E Polderman Miranda H van Triest Ruben van Boxtel Almut Schulze Wouter de Laat Edwin Cuppen Boudewijn M T Burgering |
| author_sort | Astrid Eijkelenboom |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-07T16:40:17Z |
| format | Article |
| id | doaj.art-48f775362ee44ecc836cdf8725a80db6 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:40:17Z |
| publishDate | 2013-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-48f775362ee44ecc836cdf8725a80db62024-03-03T08:20:01ZengSpringer NatureMolecular Systems Biology1744-42922013-01-0191n/an/a10.1038/msb.2012.74Genome‐wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profilingAstrid Eijkelenboom0Michal Mokry1Elzo de Wit2Lydia M Smits3Paulien E Polderman4Miranda H van Triest5Ruben van Boxtel6Almut Schulze7Wouter de Laat8Edwin Cuppen9Boudewijn M T Burgering10Department of Molecular Cancer Research, University Medical Centre Utrecht The NetherlandsHubrecht Institute for Developmental Biology and Stem Cell Research, KNAW and University Medical Centre Utrecht The NetherlandsHubrecht Institute for Developmental Biology and Stem Cell Research, KNAW and University Medical Centre Utrecht The NetherlandsDepartment of Molecular Cancer Research, University Medical Centre Utrecht The NetherlandsDepartment of Molecular Cancer Research, University Medical Centre Utrecht The NetherlandsDepartment of Molecular Cancer Research, University Medical Centre Utrecht The NetherlandsDepartment of Cell Biology, University Medical Centre Utrecht The NetherlandsGene Expression Analysis Laboratory, Cancer Research UK London Research Institute London UKHubrecht Institute for Developmental Biology and Stem Cell Research, KNAW and University Medical Centre Utrecht The NetherlandsHubrecht Institute for Developmental Biology and Stem Cell Research, KNAW and University Medical Centre Utrecht The NetherlandsDepartment of Molecular Cancer Research, University Medical Centre Utrecht The NetherlandsForkhead 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.https://doi.org/10.1038/msb.2012.74enhancerFOXOinitiationRNA pol IItranscription |
| spellingShingle | Astrid Eijkelenboom Michal Mokry Elzo de Wit Lydia M Smits Paulien E Polderman Miranda H van Triest Ruben van Boxtel Almut Schulze Wouter de Laat Edwin Cuppen Boudewijn M T Burgering Genome‐wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling Molecular Systems Biology enhancer FOXO initiation RNA pol II transcription |
| 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 | enhancer FOXO initiation RNA pol II transcription |
| url | https://doi.org/10.1038/msb.2012.74 |
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