|
| Status |
Public on Dec 31, 2012 |
| Title |
Fbxl10 regulates PRC1 recruitment to CpG islands and H2A ubiquitination |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Polycomb repressive complex 1 (PRC1) catalyzes H2A monoubiquitination (uH2A) and regulates pluripotency in embryonic stem cells (ESCs). However the mechanisms controlling PRC1 recruitment and activity are largely unknown. Here we show that Fbxl10 interacts with Ring1B and Nspc1, forming a non-canonical PRC1. We demonstrate that Fbxl10-PRC1 is essential for H2A ubiquitination in mouse ESCs. Genome-wide analyses reveal that Fbxl10 preferentially binds to CpG islands and co-localizes with Ring1B on Polycomb target genes. Notably, Fbxl10 depletion causes modest dissociation of Ring1B but a major loss of uH2A on target genes. Furthermore rescue experiments for Fbxl10 reveal that its DNA binding capability and integration into PRC1 are required for proper H2A ubiquitination. ES cells lacking Fbxl10, like previously characterized Polycomb mutants, show a severely compromised capacity for successful differentiation. Our results shed light on a novel mechanism how CpG islands regulate chromatin function by affecting polycomb recruitment and activity.
|
| |
|
| Overall design |
All ChIP-seq reactions were performed in either untransfected cells, cells expressing scrambled shRNA or Fbxl10 shRNA, Ring1b-/- or Suz12-/- mouse ES cells
|
| |
|
| Contributor(s) |
Wu X, Johansen JV |
| Citation(s) |
23395003 |
| |
| Submission date |
May 11, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Xudong Wu |
| E-mail(s) |
[email protected]
|
| Organization name |
Biotech Research and Innovation Centre
|
| Street address |
Ole Maaløes Vej 5
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
|
| Platforms (2) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (11)
|
|
| Relations |
| SRA |
SRP013052 |
| BioProject |
PRJNA166917 |
Less...
More...