Ask about this productRelated genes to: UHRF1 antibody
- Gene:
- UHRF1 NIH gene
- Name:
- ubiquitin like with PHD and ring finger domains 1
- Previous symbol:
- -
- Synonyms:
- ICBP90, Np95, FLJ21925, RNF106, TDRD22
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-03-15
- Date modifiied:
- 2017-03-17
Related products to: UHRF1 antibody
Related articles to: UHRF1 antibody
- Zygotic genome activation (ZGA) is a critical developmental milestone whose metabolic regulation remains unclear. This study identifies a pivotal role for Nicotinamide adenine dinucleotide (NAD) metabolism in regulating ZGA through poly(ADP‑ribose) polymerase 7(PARP7)-mediated ADP-ribosylation. Using ultra-low input embryo metabolomics, we profiled metabolism from zygote to blastocyst, revealing a significant NAD decline at the 2-cell stage. This shift coincided with specific upregulation of the mono-ADP-ribosyltransferase PARP7, confirmed by transcriptomics, quantitative RT-PCR, western blot, and immunofluorescence. Genetic knockdown via trim-away technology or pharmacological inhibition with RBN-2397 caused developmental delay/arrest at the 2-cell stage, impaired blastocyst formation, and defective ZGA. Mechanistically, PARP7 deficiency reduced chromatin accessibility (ATAC-seq), diminished H3K4ac and H3K27ac marks, and impaired RNA polymerase II transcription. Integrated proteomics and ADP-ribosylome analysis of late 2-cell embryos identified UHRF1 as a key PARP7 target, mono-ADP-ribosylated at lysines K30 and K31. This modification stabilized UHRF1 protein (cycloheximide chase), and UHRF1 overexpression partially rescued the transcriptional defects associated with ZGA from PARP7 inhibition. Our findings establish a metabolic-epigenetic axis wherein NAD metabolism, via PARP7-mediated ADP-ribosylation of UHRF1, regulates chromatin remodeling and transcriptional activation during ZGA, offering fundamental insights into early development. - Source: PubMed
Publication date: 2026/06/15
Cao GuangyiZhang ZiqiChen AnqiLiu YanboLin YulingYu LinaShi RuixinGuo AoleiMao YanLou GangguiLi ChaojunWen LuhongYan GuijunSun Haixiang - Cancer remains a major global health challenge, and emerging research highlights the role of the gut microbiota in cancer development. This complex microbial community supports digestion, immunity, and even mental well-being, adapting to lifestyle factors like diet and exercise. One key function is the breakdown of tryptophan (Trp) into indole. Studies have linked these compounds to cancer, inflammatory conditions, and brain disorders. This review compiles evidence showing that indole derivatives produced by gut bacteria could serve as potential anticancer agents by targeting specific biochemical pathways. Mechanistically, these metabolites inhibit IDO1, lower kynurenine levels, decrease regulatory T cells, and increase CD8+ T cell responses. They also activate tumor-suppressive signaling pathways such as the aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and nuclear factor erythroid 2-related factor 2 (NRF2), while regulating reactive oxygen species (ROS). In addition, some indole derivatives trigger interleukin-12 (IL-12)-mediated T cell activation, leading to metabolic stress in cancer cells by downregulating UHRF1 and activating AMP-activated protein kinase (AMPK), thereby depleting ATP and causing cell death. Relevant literature was identified from PubMed, Google Scholar, and Scopus up to January 2026. Collectively, understanding this link could support development of personalized diets and microbiota-based cancer therapies. - Source: PubMed
Publication date: 2026/05/28
Tomar KhushiKhodlan PallaviMalik TabarakRana PayalTariq MohdMishra RichaMohan AnandFatima SadafGautam HemantKumar SaranAbdin Malik ZainulKumar Anil - Zygotic genome activation (ZGA) is essential for initiating the developmental gene expression program in early embryos. However, whether a gating mechanism orchestrated by a limited number of factors exists in mammals remains debated. In this study, by utilizing an Nlrp14-deficient model that intriguingly disrupts the zygotic localization of UHRF1 and DNMT1, and in combination with comprehensive genetic approaches, we demonstrated that the nuclear exclusion of UHRF1 is essential for mouse ZGA and subsequent developmental progression. Mechanistically, the failure to exclude UHRF1 and DNMT1 from the nucleus in zygotes would impede DNA demethylation in LINE1 elements, promote UHRF1 binding to silence their expression, thereby reducing global chromatin accessibility and inhibiting ZGA. This effect was rescued in Uhrf1/Nlrp14 double knockout (DKO) embryos, which still exhibited heavy DNA methylation, highlighting a dispensable role of UHRF1 in the maintenance of genome-wide DNA methylation after fertilization. Furthermore, reducing DNA methylation through Dnmt1/Nlrp14 DKO or inhibiting the DNA methylation-binding domains of UHRF1 mitigated the adverse effects of nuclear-localized UHRF1 and reactivated the ZGA genes. Finally, we demonstrated that the residual nuclear UHRF1 in normal embryos binds to and facilitates the transcriptional inactivation of specific LTR subtypes that evade DNA demethylation during the genome-wide epigenetic reprogramming. Our findings not only highlight the biological significance of UHRF1 and DNMT1 nuclear exclusion but also elucidate the potentially conserved mechanism that regulates ZGA during mammalian preimplantation development. - Source: PubMed
Publication date: 2026/05/26
Yan RuiCheng XinLong XinZhu YatingZhang QianchengSun FengyuanZhang FanWang MengyueZhang RuifengGuo TianziHou XinlingJi DongmeiCao YunxiaGao FeiLiang DanGuo Fan - Alternations of DNA methylation occur in aging, which is regulated by DNA methyltransferases (DNMTs). In this study, we show that even though the transcription of DNMT1, the only enzyme that maintains DNA methylation in the mammalian genome, is reported to be decreased in an age-dependent manner, the decrease of mRNA does not result in a decrease of its protein. Instead, DNMT1 protein is increased in aged mouse tissues, which is responsible for the methylation of genes related to macroautophagy/autophagy, senescence repression, and melanin synthesis and transport in aged organs, resulting in a decline of autophagy, an increase of senescence in those organs, and a decrease in melanin production in hair follicles (canities) in response to ionizing radiation (IR). Genetic deletion and inhibition of DNMT1 can reverse these processes. The interaction of DNMT1 with ATG7 through its CXXC domain is essential for its degradation, and treatment with senolytics also downregulates DNMT1 in aged organs, supporting two feedback loops between them.: 4-OHT, 4-hydroxytamoxifen; ChIP, chromatinimmunoprecipitation; D, dasatinib; D-gal, D-galactose; DCT/Trp-2, dopachrometautomerase; DMRs, differentially methylated regions; DNAm, DNA methylation; DNMTs,DNA methyltransferases; DSBs, double-stranded breaks; ETO, etoposide; GST, glutathione-S-transferase; HEK293T,human embryonic kidney 293T; HEM, human epidermal melanocytes; Hydr, hydralazine;IP, immunoprecipitation; IR, ionizingradiation; KIF1A, kinesin family member 1A; M, methylated; MmIMCD3,mouse inner-medullary collecting duct 3; MITF, melanocyte inducingtranscription factor; MSP, methylation specific PCR; NCBI, national center for biotechnologyinformation; N-me, N-methyladenosine; PBMCs, peripheral blood mononuclear cells;Pro, proliferating; Q, quercetin; Rapa, rapamycin; RRBS, reduced representationbisulfite sequencing; RT, reverse transcription; SA-GLB1/β-Gal, senescence-associatedgalactosidase beta 1; SASP, senescence-associated secretory phenotype; Sen, senescent; SNP, single nucleotidepolymorphism; TYR, tyrosinase; TYRP1/Trp-1, tyrosinase related protein 1; UHRF1,ubiquitin like with PHD and ring finger domains 1; UM, unmethylated; UTR, untranslatedregion; WGBS, whole-genome bisulfite sequencing. - Source: PubMed
Publication date: 2026/05/28
Li LuMao XinyueLi Linda XiaoyanXiao HuapingLou ZhenkunLiu HongboZhou Julie XiaYao LiLi Xiaogang - Ubiquitin-like with plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) is essential for DNA methylation inheritance. However, the functional impacts of several natural and engineered UHRF1 variants are either insufficiently characterized or obscured by conflicting results, with some discrepancies likely stemming from cellular toxicity and adaptive responses induced by DNA methylation changes. In this study, we utilized mouse embryonic stem cells (mESCs)-which uniquely tolerate the complete loss of DNA methylation-to evaluate the functional consequences of clinical mutations, isoform variation, and epitope tagging. Using rescue experiments in Uhrf1-deficient mESCs, we characterized two UHRF1 mutations identified in a patient with immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, demonstrating that the R618X nonsense mutation creates a null allele, while the R296W missense mutation is hypomorphic. Furthermore, we confirmed that N-terminal tagging abolishes UHRF1 function, whereas human UHRF1 (hUHRF1) isoform 2, featuring a 13-residue N-terminal extension, is functionally inactive. AlphaFold3 structural predictions suggest that these additional residues at the N terminus disrupt essential inter-domain interactions. Collectively, our results define the activity of UHRF1 variants and resolve existing inconsistencies in the field. - Source: PubMed
Publication date: 2026/05/14
Liu BigangNayvelt KailaHardikar SwanandKondo KimieEstecio Marcos RCheng XiaodongChen Taiping