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| Status |
Public on Apr 30, 2019 |
| Title |
Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency. (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The mechanisms underlying enhancer activation and the extent to which enhancer-promoter rewiring contributes to spatiotemporal gene expression are not well understood. Using integrative and time resolved analyses we show that the extensive transcriptome and epigenome resetting during the conversion between ‘serum-’ and ‘2i’-states of mouse embryonic stem cells (ESCs) takes place with minimal enhancer-promoter rewiring that becomes more evident in primed-state pluripotency. Instead, differential gene expression is strongly linked to enhancer activation via H3K27ac. Conditional depletion of TFs and allele-specific enhancer analysis reveals an essential role for Esrrb in H3K27-acetylation and activation of 2i-specific enhancers. Restoration of a polymorphic ESRRB motif using CRISPR/Cas9 in a hybrid ESC-line, restores ESRRB binding and enhancer H3K27ac in an allele-specific manner but has no effect on chromatin interactions. Our study shows that enhancer activation in serum- and 2i-ESCs is largely driven by TF-binding and epigenetic marking in a hardwired network of chromatin interactions.
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| Overall design |
ChIP-seq analysis of H3K27ac, ESRRB, GFP, CTCF, YY1, SMC1 in E14- or F1-ESCs cultured in 2i, serum or EpiLSC medium. ChIP-seq analysis for H3K27ac in Tamoxifen inducible Nr5a2 or Esrrb- KO ESCs.
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| Citation(s) |
31036938 |
| |
| Submission date |
Dec 14, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Hendrik G Stunnenberg |
| E-mail(s) |
h.stunnenberg@ncmls.ru.nl
|
| Organization name |
Radboud University
|
| Street address |
Geert Grooteplein 30
|
| City |
Nijmegen |
| ZIP/Postal code |
6525GA |
| Country |
Netherlands |
| |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (61)
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| This SubSeries is part of SuperSeries: |
| GSE92412 |
Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency. |
|
| Relations |
| BioProject |
PRJNA357480 |
| SRA |
SRP095132 |
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