|
| Status |
Public on Nov 18, 2022 |
| Title |
Multiple signalling pathways converge on UHRF1 stability and activity |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Propagation of DNA methylation through cell division relies on the recognition of methylated cytosines by UHRF1. We present an experimental system where regulation of global and site-specific demethylation can be dissected in great detail, which is part of the biology of stem cells transitioning to ground state pluripotency upon signal inhibition. In this study we begin to elucidate the signalling pathways that converge upon UHRF1 regulation by employing a high-throughput shRNA screen targeting genes of the mouse kinome, using UHRF1-GFP fluorescence as readout. Our screen identified a total of 251 genes, enriched in factors related to metabolic processes. We found that whilst all candidates tested rescued UHRF1 from proteasomal degradation, UHRF1 in Nags and Csnk2b knockdown prevented DNA methylation loss, whereas in Prpsap2 and Sephs2 knockdown cells UHRF1 activity was impaired leading to methylation loss. This study, therefore, provides a valuable resource for understanding the interface between signalling and its effect on the epigenome
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| |
|
| Overall design |
shRNA screen to identify kinases regulating UHRF1
|
| |
|
| Contributor(s) |
Rushton MD, Ficz G |
| Citation(s) |
35324392 |
| |
| Submission date |
Sep 23, 2020 |
| Last update date |
Nov 18, 2022 |
| Contact name |
Gabriella Ficz |
| E-mail(s) |
g.ficz@qmul.ac.uk, gabriella.ficz@googlemail.com
|
| Phone |
07557774595
|
| Organization name |
Barts Cancer Institute, Queen Mary University of London
|
| Street address |
Centre for Haemato-Oncology
|
| City |
London |
| State/province |
Rest of the World |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA665250 |
| SRA |
SRP285128 |
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