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| Status |
Public on Oct 26, 2017 |
| Title |
Poised enhancers regulatory activity is topologically facilitated by polycomb [RNA-seq LHX5] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology.
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| Overall design |
mRNA profiles were generated by RNA-seq from AntNPC derived from mESC: WT AntNPC (four biological replicates), PE Lhx5(-109)-/- Clon1 AntNPC (two biological replicates) and PE Lhx5(-109)-/- Clon2 AntNPC (two biological replicates).
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| Contributor(s) |
Cruz-Molina S, Nikolic M, Rada-Iglesias A |
| Citation(s) |
28285903 |
| |
| Submission date |
Oct 27, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Milos Nikolic |
| E-mail(s) |
milosn@gmail.com
|
| Organization name |
Center for Molecular Medicine Cologne
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| Street address |
Robert Koch Str. 21
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| City |
Koeln |
| State/province |
Nordrhein-Westfalen |
| ZIP/Postal code |
50674 |
| Country |
Germany |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE89211 |
PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation |
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| Relations |
| BioProject |
PRJNA350821 |
| SRA |
SRP092184 |
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