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Status |
Public on Aug 13, 2013 |
Title |
FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
FOXO transcription factors are central regulators of longevity from worms to humans. FOXO3 – the FOXO isoform associated with exceptional human longevity – preserves adult neural stem cell pools. Here we identify FOXO3 direct targets genome-wide in primary cultures of adult neural progenitor cells (NPCs). Interestingly, FOXO3-bound sites are enriched for motifs for bHLH transcription factors and FOXO3 shares common targets with the pro-neuronal bHLH transcription factor ASCL1/MASH1 in NPCs. Analysis of the chromatin landscape reveals that FOXO3 and ASCL1 are particularly enriched at the enhancers of genes involved in neurogenic pathways. Intriguingly, FOXO3 inhibits ASCL1-dependent neurogenesis in NPCs and direct neuronal conversion in fibroblasts. FOXO3 also restrains neurogenesis in vivo. Our study identifies a genome-wide interaction between the pro-longevity transcription factor FOXO3 and the cell fate determinant ASCL1, and raises the possibility that FOXO3’s ability to restrain ASCL1-dependent neurogenesis may help preserve the neural stem cell pool.
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Overall design |
ChIP-seq profiles of two transcription factors (FOXO3 and ASCL1) and three histone marks (H3K4me1, H3K4me3 and H3K27me3) in adult mouse neural progenitor cells.
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Contributor(s) |
Brunet A |
Citation(s) |
23891001 |
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Submission date |
Jun 26, 2013 |
Last update date |
May 15, 2019 |
Contact name |
Anne Brunet |
Organization name |
Stanford University
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Department |
Genetics
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Street address |
300 Pasteur Drive,
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City |
Stanford |
State/province |
California |
ZIP/Postal code |
94305 |
Country |
USA |
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Platforms (1) |
GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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Samples (7)
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Relations |
BioProject |
PRJNA209713 |
SRA |
SRP026343 |