Recombinant Mouse E3 ubiquitin-protein ligase UHRF1 (Uhrf1)

1. Epigenetic enhancement of the post-replicative DNA mismatch repair of mammalian genomes by a Hemi-(m)CpG-Np95-Dnmt1 axis has been demonstrated for humans and mice. PMID: 27886214
2. These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation. PMID: 29180567
3. UHRF1 ubiquitinates PAF15 at Lys 15 and Lys 24 and promotes its binding to PCNA during late S-phase PMID: 29055779
4. Whole genome bisulfite sequencing revealed that blastocysts derived from KO oocytes have a greatly reduced level of CG methylation, suggesting that maternal UHRF1 is essential for maintaining CG methylation, particularly at the imprinting control regions, in preimplantation embryos. PMID: 28976982
5. SETDB1 maintains silencing of intracisternal A particle, but in the absence of DNMT1, prolonged binding of NP95 to hemimethylated DNA transiently disrupts SETDB1-dependent H3K9me3 deposition. PMID: 27151458
6. deletion of Uhrf1 lead to global DNA hypomethylation with a strong activation of the intracisternal A particle (IAP) family of endogenous retroviral elements, accompanied by an increase in 5-hydroxymethylcytosine PMID: 27798843
7. Our results provide insights into the molecular basis of DNMT1 dysfunction in hereditary sensory and autonomic neuropathies with dementia and hearing loss patients and emphasize the importance of the TS domain in the regulation of DNA methylation in pluripotent and differentiating cells PMID: 28334952
8. results identify UHRF1 as a novel HSP90 client protein and shed light on the regulation of UHRF1 stability and function. PMID: 27489107
9. Uhrf1 regulation of the Akt-mTOR signaling pathway is required for invariant natural killer T cell development. PMID: 27050515
10. Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its H3 histone recognition. PMID: 27045799
11. the histone modification status at the DMRs of imprinted genes may dictate whether DNA methylation could be restored upon UHRF1 re-expression PMID: 25900245
12. UHRF1 is strongly up-regulated during liver regeneration independently of BIRC5. PMID: 24818710
13. report identifies PARP1 as a novel modulator of two UHRF1-regulated heterochromatin-associated events: the accumulation of H4K20me3 and the clearance of DNMT1 PMID: 24782312
14. Uhrf1 deficiency resulted in derepression of the gene (Cdkn1a) that encodes the cyclin-dependent kinase inhibitor p21 due to hypomethylation of its promoter region, which resulted in cell-cycle arrest of Treg cells. PMID: 24777532
15. These findings show that apart from the targeting of DNMT1 to the replicated DNA UHRF1 increases the activity and specificity of DNMT1, thus exerting a multifaceted influence on the maintenance of DNA methylation. PMID: 24368767
16. The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA. PMID: 24253042
17. UHRF1 can target DNMT1 for DNA maintenance methylation through binding either histone 3 lysine 9 methylation 2/3 or hemi-methylated CpG. PMID: 23463006
18. The UHRF1 is not functionally redundant in DNA methylation maintenance and reveals the cell-cycle-dependent interaction between UHRF1 and DNMT1 as a key regulatory mechanism targeting DNMT1 for DNA methylation. PMID: 22064703
19. results reveal that the disruption of Dnmt1/PCNA/UHRF1 interactions acts as an oncogenic event and that one of its signatures (i.e. the low level of mMTase activity) is a molecular biomarker associated with a poor prognosis in GBM patients PMID: 20613874
20. Np95, Dnmt3a and Dnmt3b in mediating epigenetic silencing through histone modification followed by DNA methylation PMID: 19798101
21. Np95 is specifically induced in terminally differentiated mouse 3T3 cells in vitro by adenovirus E1A proteins and is essential for S phase entry. PMID: 12058012
22. NP95 functions as a common component in the multiple response pathways against DNA damage and replication arrest and thereby contributes to genomic stability. PMID: 12084726
23. Np95 is a chromatin-associated ubiquitin ligase that binds to histones in vivo and in vitro PMID: 14993289
24. Np95 is a new relevant protein involved in heterochromatin replication and formation. PMID: 17182844
25. data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation PMID: 17673620
26. Np95 is essential in vivo to maintain global and local DNA methylation and to repress transcription of retrotransposons and imprinted genes PMID: 17994007
27. the PHD domain of Np95-ICBP90 contributes to the opening and/or stabilization of dense chromocenter structures to support the recruitment of modifying enzymes, like HDAC and DNMT1, required for the replication and formation of PH PMID: 18508923
28. These findings link Eme1 with the replication-associated chromatin modifier functions of Np95 in the cellular response to DNA damage. PMID: 18692478
29. Crystal structure; UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA PMID: 18772888
30. the crystal structures of the SET and RING-associated (SRA) domain of Uhrf1 in free and hemi-methylated DNA-bound states PMID: 18772891
31. UHRF1 recruited and cooperated with G9a to inhibit the p21 promoter activity, which correlated with the elevated p21 protein level in murine Uhrf1-null embryonic stem cells. PMID: 19056828
32. UHRF1 may bring two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication PMID: 19077538
33. UHRF1 inhibits the late phase of oligodendrocyte differentiation. PMID: 17065439

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KEGG: mmu:18140

STRING: 10090.ENSMUSP00000001258

UniGene: Mm.42196