biostudies-literatureRushton MDMedical Research Council1590-1607https://www.ebi.ac.uk/biostudies/studies/S-EPMC9621053biostudies-literatureUnknown17(12)Propagation of DNA methylation through cell division relies on the recognition of methylated cytosines by UHRF1. In reprogramming of mouse embryonic stem cells to naive pluripotency (also known as ground state), despite high levels of <i>Uhrf1</i> transcript, the protein is targeted for degradation by the proteasome, leading to DNA methylation loss. We have undertaken an shRNA screen to identify the signalling pathways that converge upon UHRF1 and control its degradation, using UHRF1-GFP fluorescence as readout. Many candidates we identified are key enzymes in regulation of glucose metabolism, nucleotide metabolism and Pi3K/AKT/mTOR pathway. Unexpectedly, while downregulation of all candidates we selected for validation rescued UHRF1 protein levels, we found that in some of the cases this EpigeneticsAn shRNA kinase screen identifies regulators of UHRF1 stability and activity in mouse embryonic stem cells.PMC9621053MR/M01892X/1Rushton MDPatani HSaunderson EAGreen MRFicz GfalseAn shRNA kinase screen identifies regulators of UHRF1 stability and activity in mouse embryonic stem cells.Propagation of DNA methylation through cell division relies on the recognition of methylated cytosines by UHRF1. In reprogramming of mouse embryonic stem cells to naive pluripotency (also known as ground state), despite high levels of <i>Uhrf1</i> transcript, the protein is targeted for degradation by the proteasome, leading to DNA methylation loss. We have undertaken an shRNA screen to identify the signalling pathways that converge upon UHRF1 and control its degradation, using UHRF1-GFP fluorescence as readout. Many candidates we identified are key enzymes in regulation of glucose metabolism, nucleotide metabolism and Pi3K/AKT/mTOR pathway. Unexpectedly, while downregulation of all candidates we selected for validation rescued UHRF1 protein levels, we found that in some of the cases this 2022-01-01T00:00:00Z2022 Dec2026-04-08T11:38:02.533Z2025-04-19T22:45:29.592ZS-EPMC96210533532439210.1080/15592294.2022.2044126