|
| Status |
Public on Jun 18, 2019 |
| Title |
Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2 |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Oct4, along with Sox2 and Klf4 (SK), can induce pluripotency but structurally similar factors like Oct6 cannot. To decode why Oct4 has this unique ability, we compare Oct4-binding, accessibility patterns and transcriptional waves with Oct6 and an Oct4 mutant defective in the dimerization with Sox2 (Oct4defSox2). We find that initial silencing of the somatic program proceeds indistinguishably with or without Oct4. Oct6 mitigates the mesenchymal-to-epithelial transition and derails reprogramming. These effects are a consequence of differences in genome-wide binding, as the early binding profile of Oct4defSox2 resembles Oct4, whilst Oct6 does not bind pluripotency enhancers. Nevertheless, in the Oct6-SK condition many otherwise Oct4-bound locations become accessible but chromatin opening is compromised when Oct4defSox2 occupies these sites. We find that Sox2 predominantly facilitates chromatin opening, whilst Oct4 serves an accessory role. Formation of Oct4/Sox2 heterodimers is essential for pluripotency establishment; however, reliance on Oct4/Sox2 heterodimers declines during pluripotency maintenance.
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| |
|
| Overall design |
GSE103978[CHIP-Seq]
GSE103979[RNA-Seq]
GSE119396[ATAC-Seq]
|
| |
|
| Citation(s) |
31375664 |
| |
| Submission date |
Sep 18, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Veeramohan Veerapandian |
| E-mail(s) |
veeramohan.v@mpi-muenster.mpg.de
|
| Organization name |
Max Planck Institute for Molecular Biomedicine
|
| Department |
Department Tissue Morphogenesis
|
| Street address |
Röntgenstr. 20
|
| City |
Munster |
| State/province |
North Rhine-Westphalia |
| ZIP/Postal code |
48149 |
| Country |
Germany |
| |
|
| Platforms (2) |
|
| Samples (71)
|
|
| This SuperSeries is composed of the following SubSeries: |
| GSE103978 |
Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2 [CHIP-Seq] |
| GSE103979 |
Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2 [RNA-Seq] |
| GSE119396 |
Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2 [ATAC-Seq] |
|
| Relations |
| BioProject |
PRJNA407838 |
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