Similar Datasets
Project description:Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks. Results: Deletion of Prmt1 in mature cells resulted in the immediate loss of H4R3me2a which induced cell dedifferentiation and cell selective Prmt1 knock-out mice developed diabetes phenotype. H4R3me2a worked as an active histone code that increased chromatin accessibility at the binding sites for transcription factors including CTCF, NKX6.1, MAFA, PDX1 and NEUROD1. Conclusions: PRMT1-dependent open chromatin regions showed a strong association with the risk of diabetes in human. In conclusion, PRMT1 plays an essential role in maintaining β cell identity by regulating chromatin accessibility.
2020-12-03 | GSE117097 | GEO
Project description:Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks. Results: Deletion of Prmt1 in mature cells resulted in the immediate loss of H4R3me2a which induced cell dedifferentiation and cell selective Prmt1 knock-out mice developed diabetes phenotype. H4R3me2a worked as an active histone code that increased chromatin accessibility at the binding sites for transcription factors including CTCF, NKX6.1, MAFA, PDX1 and NEUROD1. Conclusions: PRMT1-dependent open chromatin regions showed a strong association with the risk of diabetes in human. In conclusion, PRMT1 plays an essential role in maintaining β cell identity by regulating chromatin accessibility.
2020-12-03 | GSE117096 | GEO
Project description:Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks. Results: Deletion of Prmt1 in mature cells resulted in the immediate loss of H4R3me2a which induced cell dedifferentiation and cell selective Prmt1 knock-out mice developed diabetes phenotype. H4R3me2a worked as an active histone code that increased chromatin accessibility at the binding sites for transcription factors including CTCF, NKX6.1, MAFA, PDX1 and NEUROD1. Conclusions: PRMT1-dependent open chromatin regions showed a strong association with the risk of diabetes in human. In conclusion, PRMT1 plays an essential role in maintaining β cell identity by regulating chromatin accessibility.
2020-12-03 | GSE117099 | GEO
Project description:PRMT1-dependent histone arginine methylation regulates mature beta cell identity
| PRJNA481040 | ENA
Project description:PRMT1-dependent histone arginine methylation regulates mature beta cell identity (ATAC-Seq)
| PRJNA481045 | ENA
Project description:PRMT1-dependent histone arginine methylation regulates mature beta cell identity (ChIP-Seq)
| PRJNA481044 | ENA
Project description:PRMT1-dependent histone arginine methylation regulates mature beta cell identity (RNA-Seq)
| PRJNA481043 | ENA
Project description:Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is implicated in modulation of cellular processes including gene transcription. The role of PRMTs in the regulation of intracellular signaling pathways has remained obscure, however. We now show that PRMT1 methylates apoptosis signal-regulating kinase 1 (ASK1) at arginine residues 78 and 80 and thereby negatively regulates ASK1 signaling. PRMT1-mediated ASK1 methylation attenuated the H(2)O(2)-induced stimulation of ASK1, with this inhibitory effect of PRMT1 being abolished by replacement of arginines 78 and 80 of ASK1 with lysine. Furthermore, depletion of PRMT1 expression by RNA interference potentiated H(2)O(2)-induced stimulation of ASK1. PRMT1-mediated ASK1 methylation promoted the interaction between ASK1 and its negative regulator thioredoxin, whereas it abrogated the association of ASK1 with its positive regulator TRAF2. Moreover, PRMT1 depletion potentiated paclitaxel-induced ASK1 activation and apoptosis in human breast cancer cells. Together, our results indicate that arginine methylation of ASK1 by PRMT1 contributes to the regulation of stress-induced signaling that controls a variety of cellular events including apoptosis.
| S-EPMC3321625 | biostudies-literature
Project description:PRMT1 is the major Arginine methyltransferase in mammalian cells and its over-expression in human cancer has been linked to poor response to cancer therapy. Here, combining mass spectrometry-based global methyl-proteomics with genome-wide mRNA expression profiling, we identify PRMT1 and its associated Arginine methylation as a regulatory hubs controlling cancer cell response to replicative stress agents. We show that DNA-PK binds to PRMT1 and regulates both its subcellular localization and activity, leading to PRMT1 recruitment to drug-stalled replication forks and channelling its methyl-transferase activity from its soluble targets towards Arginine 3 of histone H4. This DNA-PK-PRMT1 axis is required for the induction of the Senescence-Associated Secretory Phenotype, which sustains cell cycle arrest and protects cells from apoptosis. Our data show that Arginine-methylation regulates the adaptive response of cancer cell to replicative stress agents and might be targeted to sensitize cancer cells to genotoxic chemotherapeutics
2020-01-14 | GSE106609 | GEO
Project description:Stress granules (SGs) are discrete assemblies of stalled messenger ribonucleoprotein complexes (mRNPs) that form when eukaryotic cells encounter environmental stress. RNA-binding proteins (RBPs) mediate their condensation by recruiting populations of mRNPs. However, the cellular and molecular mechanisms underlying the role of ubiquitin-associated protein 2-like (UBAP2L) in the regulation of SG dynamics remain elusive. Here, we show that UBAP2L is required for both SG assembly and disassembly. UBAP2L overexpression nucleated SGs under stress-null conditions. The UBAP2L Arg-Gly-Gly (RGG) motif was required for SG competence, and mediated the recruitment of SG components, including mRNPs, RBPs, and ribosomal subunits. The domain of unknown function (DUF) of UBAP2L-mediated interaction with ras GTPase-activating protein-binding protein (G3BP)1/2, and its deletion caused the cytoplasmic-nuclear transport of UBAP2L and G3BP1/2, thereby compromising SG formation. The protein arginine methyltransferase PRMT1 asymmetrically dimethylated UBAP2L by targeting the RGG motif. Increased arginine methylation blocked, whereas its decrease enhanced UBAP2L interactions with SG components, ablating and promoting SG assembly, respectively. These results provide new insights into the mechanisms by which UBAP2L regulates SG dynamics and RNA metabolism.
| S-EPMC7205891 | biostudies-literature