|
| Status |
Public on Nov 26, 2013 |
| Title |
FOXO3 selectively amplifies enhancer activity to establish target gene regulation. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Forkhead Box O (FOXO) transcription factors are versatile players in diverse cellular processes, affecting tumorigenesis, metabolism, stem cell maintenance and lifespan. To understand the transcriptional output of FOXO3 activation, we investigate features that define the subset of enhancer binding events that actually contribute to gene regulation. We show FOXO3 transcriptional output is determined by the amount of bound FOXO3, which in turn is determined by motif presence, pre-existing enhancer activity and accessibility. In this manner, FOXO3 amplifies pre-existing levels of activity marks and potentiates enhancer RNA transcription. We conclude that not only enhancer presence and sequence content, but also the pre-existing activity dictates FOXO3 binding and transcriptional output. Considering the flexible and cell type specific nature of regulatory regions and their activity, our observations provide a novel explanation for the diversity in FOXO transcriptional programs and introduce chromatin context as a new player in the regulation of FOXO activity in ageing and disease.
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| |
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| Overall design |
Examination of histone modifications and transcriptome changes upon FOXO activation
|
| |
|
| Contributor(s) |
Mokry M |
| Citation(s) |
24360957 |
| Submission date |
Aug 27, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Michal Mokry |
| E-mail(s) |
m.mokry@umcutrecht.nl
|
| Organization name |
Wilhelmina Children's Hospital, University Medical Center Utrecht
|
| Street address |
Lundlaan 6
|
| City |
Utrecht |
| ZIP/Postal code |
3584 EA |
| Country |
Netherlands |
| |
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| Platforms (1) |
| GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
|
| Samples (18)
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| Relations |
| BioProject |
PRJNA217329 |
| SRA |
SRP029259 |
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