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UHRF1

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https://www.readbyqxmd.com/read/29449903/specific-or-not-specific-recruitment-of-dnmts-for-dna-methylation-an-epigenetic-dilemma
#1
REVIEW
Eric Hervouet, Paul Peixoto, Régis Delage-Mourroux, Michaël Boyer-Guittaut, Pierre-François Cartron
Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29415984/uhrf1-depletion-sensitizes-retinoblastoma-cells-to-chemotherapeutic-drugs-via-downregulation-of-xrcc4
#2
Heng He, Chunsik Lee, Jong Kyong Kim
UHRF1 (ubiquitin-like with PHD and ring finger domains 1) is highly expressed in various human cancers including retinoblastoma, and associated with tumor-promoting effects such as inhibition of apoptosis and high proliferation. However, the molecular mechanisms underlying tumor-promoting functions of UHRF1 in retinoblastoma still remain elusive. Here, we show that stable knockdown of UHRF1 renders retinoblastoma cells sensitized to conventional chemotherapeutic drugs such as etoposide and camptothecin, resulting in enhanced DNA damage and apoptotic cell death...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29395786/an-intramolecular-interaction-of-uhrf1-reveals-dual-control-for-its-histone-association
#3
Linfeng Gao, Xiao-Feng Tan, Shen Zhang, Tianchen Wu, Zhi-Min Zhang, Hui-Wang Ai, Jikui Song
UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR). Structural analysis reveals that PBR binding leads to displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded UHRF1 conformation...
January 18, 2018: Structure
https://www.readbyqxmd.com/read/29285183/targeting-microrna-uhrf1-pathways-as-a-novel-strategy-for-cancer-therapy
#4
Hani Choudhry, Mazin A Zamzami, Ziad Omran, Wei Wu, Marc Mousli, Christian Bronner, Mahmoud Alhosin
Ubiquitin-like containing plant homeodomain and RING finger domains 1 (UHRF1) is an anti-apoptotic protein involved in the silencing of several tumor suppressor genes (TSGs) through epigenetic modifications including DNA methylation and histone post-translational alterations, and also epigenetic-independent mechanisms. UHRF1 overexpression is observed in a number of solid tumors and hematological malignancies, and is considered a primary mechanism in inhibiting apoptosis. UHRF1 exerts its inhibitory activity on TSGs by binding to functional domains and therefore influences several epigenetic actors including DNA methyltransferase, histone deacetylase 1, histone acetyltransferase Tat-interacting protein 60 and histone methyltransferases G9a and Suv39H1...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29262320/the-arginine-methyltransferase-prmt6-regulates-dna-methylation-and-contributes-to-global-dna-hypomethylation-in-cancer
#5
Nicolas Veland, Swanand Hardikar, Yi Zhong, Sitaram Gayatri, Jiameng Dan, Brian D Strahl, Scott B Rothbart, Mark T Bedford, Taiping Chen
DNA methylation plays crucial roles in chromatin structure and gene expression. Aberrant DNA methylation patterns, including global hypomethylation and regional hypermethylation, are associated with cancer and implicated in oncogenic events. How DNA methylation is regulated in developmental and cellular processes and dysregulated in cancer is poorly understood. Here, we show that PRMT6, a protein arginine methyltransferase responsible for asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a), negatively regulates DNA methylation and that PRMT6 upregulation contributes to global DNA hypomethylation in cancer...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29234018/dynamics-of-rif1-sumoylation-is-regulated-by-pias4-in-the-maintenance-of-genomic-stability
#6
Ramesh Kumar, Cheok Chit Fang
RIF1 plays a key role in inhibiting DNA end resection and promoting NHEJ mediated DNA double stand break repair in G1. However, whether SUMOlyation may regulate RIF1 functions is still largely unknown. Here, we report that RIF1 is SUMOlyated in response to DNA damage. We identified PIAS4 as the primary SUMO E3 ligase required for the SUMOylation of RIF1 protein. Mammalian cells compromised of PIAS4 expression, show impaired RIF1 SUMOylation and defective for the disassembly of DNA damage responsive RIF1 foci...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29187878/uhrf1-is-an-independent-prognostic-factor-and-a-potential-therapeutic-target-of-esophageal-squamous-cell-carcinoma
#7
Jiecheng Ye, Yong Zhang, Weiye Liang, Jianxian Huang, Lihui Wang, Xueyun Zhong
Purpose: Ubiquitin-like with plant homeodomain and ring-finger domains 1 (UHRF1) plays an essential role in DNA methylation, and the overexpression of UHRF1 is associated with poor prognosis in various cancers. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of esophageal cancer cases in China, but the five-year survival rate for patients is less than 10% due to limited clinical approaches for early diagnosis and treatment. The present research aimed to investigate the expression of UHRF1 in ESCC and its biological role in ESCC development...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29180567/uhrf1-is-indispensable-for-normal-limb-growth-by-regulating-chondrocyte-differentiation-through-specific-gene-expression
#8
Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, Yuuki Imai
Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1ΔLimb/ΔLimb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation...
November 27, 2017: Development
https://www.readbyqxmd.com/read/29168472/characterization-of-naturally-occurring-pentacyclic-triterpenes-as-novel-inhibitors-of-deubiquitinating-protease-usp7-with-anticancer-activity-in-vitro
#9
Bo Jing, Meng Liu, Li Yang, Hai-Yan Cai, Jie-Bo Chen, Ze-Xi Li, Xi Kou, Yun-Zhao Wu, Dong-Jun Qin, Li Zhou, Jin Jin, Hu Lei, Han-Zhang Xu, Wei-Wei Wang, Ying-Li Wu
Deubiquitinating protease USP7 is a promising therapeutic target for cancer treatment, and interest in developing USP7 inhibitors has greatly increased. In the present study, we reported a series of natural pentacyclic triterpenes with USP7 inhibitory activity in vitro. Among them, both the ursane triterpenes and oleanane triterpenes were more active than the lupine triterpenes, whereas ursolic acid was the most potent with IC50 of 7.0±1.5 μmol/L. Molecular docking studies showed that ursolic acid might occupy the ubiquitin binding pocket of USP7, with the 17-carboxyl group and 3-hydroxyl group playing a vital role in the USP7-ursolic acid interaction...
November 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29157076/uhrf1-epigenetically-down-regulates-ubch8-to-inhibit-apoptosis-in-cervical-cancer-cells
#10
Qishu Zhang, Lijun Qiao, Xiao Wang, Changkuan Ding, Jason J Chen
UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is an important epigenetic regulator that plays a part in DNA methylation, protein methylation and ubiquitination. It is also frequently overexpressed in many types of cancers, including cervical cancer, which is caused by human papillomavirus (HPV). In this study, we showed that UHRF1 was up-regulated in HPV oncogene E7 expressing cells and HPV-positive cervical cancer cells. We demonstrated that UHRF1 down-regulated the expression of UBE2L6 gene that encodes the ISG15-conjugating enzyme UbcH8...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29074623/conformational-dynamics-of-the-ttd-phd-histone-reader-module-of-uhrf1-reveals-multiple-histone-binding-states-allosteric-regulation-and-druggability
#11
R Scott Houliston, Alexander Lemak, Aman Iqbal, Danton Ivanochko, Shili Duan, Lilia Kaustov, Michelle S Ong, Lixin Fan, Guillermo Senisterra, Peter J Brown, Yun-Xing Wang, Cheryl H Arrowsmith
UHRF1 is a key mediator of inheritance of epigenetic DNA methylation patterns during cell division and is a putative target for cancer therapy. Recent studies indicate that interdomain interactions critically influence UHRF1's chromatin-binding properties, including allosteric regulation of its histone binding. Here, using an integrative approach that combines small angle X-ray scattering (SAXS), NMR spectroscopy, and molecular dynamics (MD) simulations, we characterized the dynamics of the TTD-PHD histone reader module, including its 20-residue interdomain linker...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29055779/ubiquitome-analysis-reveals-pcna-associated-factor-15-paf15-as-a-specific-ubiquitination-target-of-uhrf1-in-embryonic-stem-cells
#12
Elisabeth Karg, Martha Smets, Joel Ryan, Ignasi Forné, Weihua Qin, Christopher B Mulholland, Georgia Kalideris, Axel Imhof, Sebastian Bultmann, Heinrich Leonhardt
Ubiquitination is a multifunctional posttranslational modification controlling the activity, subcellular localization and stability of proteins. The E3 ubiquitin ligase UHRF1 is an essential epigenetic factor that recognizes repressive histone marks as well as hemi-methylated DNA and recruits DNMT1. To explore enzymatic functions of UHRF1 beyond epigenetic regulation we conducted a comprehensive screen in mouse embryonic stem cells to identify novel ubiquitination targets of UHRF1 and its paralogue UHRF2. We found differentially ubiquitinated peptides associated with a variety of biological processes such as transcriptional regulation and DNA damage response...
October 18, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28981102/regulation-of-rip3-by-the-transcription-factor-sp1-and-the-epigenetic-regulator-uhrf1-modulates-cancer-cell-necroptosis
#13
Chengkui Yang, Jun Li, Lu Yu, Zili Zhang, Feng Xu, Lang Jiang, Xiuxia Zhou, Sudan He
Receptor-interacting kinase-3 (RIP3) is a key regulator of necroptosis. It has been shown that the expression of RIP3 is silenced in most cancer cells and tissues due to genomic methylation. However, the regulatory mechanisms controlling RIP3 expression in cancer cells have not been fully elucidated. Here, we report that Sp1, a well-characterized zinc-finger transcription factor, directly regulates RIP3 expression in cancer cells. Knockdown of endogenous Sp1 significantly decreases the transcription of Rip3, thereby further inhibiting necroptosis...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28976982/role-of-uhrf1-in-de-novo-dna-methylation-in-oocytes-and-maintenance-methylation-in-preimplantation-embryos
#14
Shoji Maenohara, Motoko Unoki, Hidehiro Toh, Hiroaki Ohishi, Jafar Sharif, Haruhiko Koseki, Hiroyuki Sasaki
The methylation of cytosine at CG sites in the mammalian genome is dynamically reprogrammed during gametogenesis and preimplantation development. It was previously shown that oocyte-derived DNMT1 (a maintenance methyltransferase) is essential for maintaining and propagating CG methylation at imprinting control regions in preimplantation embryos. In mammalian somatic cells, hemimethylated-CG-binding protein UHRF1 plays a critical role in maintaining CG methylation by recruiting DNMT1 to hemimethylated CG sites...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28976514/role-of-epigenetic-regulation-on-the-induction-of-apoptosis-in-jurkat-leukemia-cells-by-white-grape-pomace-rich-in-phenolic-compounds
#15
Antonio J León-González, M José Jara-Palacios, Malak Abbas, Francisco J Heredia, Valérie B Schini-Kerth
Grape pomace is a rich source of phenolic compounds commonly employed for elaboration of dietary supplements. The aim of the present study was to investigate the anticancer effect of a purified white grape pomace extract (PWGPE) in acute lymphoblastic leukemia Jurkat cells and to characterize the underlying mechanism. Apoptosis, mitochondrial membrane potential and reactive oxygen species (ROS) levels were assessed by flow cytometry and protein expression levels were analysed by Western blotting. PWGPE induced apoptosis in Jurkat cells in a time- and concentration-dependent manner...
October 4, 2017: Food & Function
https://www.readbyqxmd.com/read/28901497/regulation-of-uhrf1-by-microrna-378-modulates-medulloblastoma-cell-proliferation-and-apoptosis
#16
Zhen-Yu Zhang, Bin Zhu, Xin-Wei Zhao, Yun-Bo Zhan, Jian-Ji Bao, Jin-Qiao Zhou, Feng-Jiang Zhang, Bin Yu, Jun Liu, Yan-Min Wang, Ya-Hui Bai, Jin Hong, Xian-Zhi Liu
A previous study revealed that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) promoted cell proliferation and was a potential biomarker in medulloblastoma (MB). In the present study, we reported that miR-378 inhibited the expression of UHRF1 to affect the proliferation of MB through competitive binding to the same region of its 3'-UTR. We found that the expression of miR-378 was significantly downregulated in MB tissues and inversely correlated with the expression of UHRF1. Western blot analysis revealed that overexpression of miR-378 led to the suppression of UHRF1...
November 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901428/emodin-promotes-the-arrest-of-human-lymphoma-raji-cell-proliferation-through-the-uhrf1%C3%A2-dnmt3a%C3%A2-%C3%A2-np73-pathways
#17
Yun Lin, Weiming Chen, Zhihong Wang, Pengwei Cai
Emodin is an active constituent found in the roots and rhizomes of numerous Chinese medicinal herbs. It exerts antitumor activity against Dalton's lymphoma in vivo, although the detailed mechanisms by which emodin induces apoptosis remains to be elucidated. The present study aimed to analyze the mechanisms underlying the response to emodin treatment. Using lymphoma Raji cells, an emodin‑induced cell proliferating inhibition model was first established, then flow cytometry, western blotting, reverse transcription‑quantitative polymerase chain reaction and luciferase reporter assay were performed...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28881702/the-epigenetic-integrator-uhrf1-on-the-road-to-become-a-universal-biomarker-for-cancer
#18
REVIEW
Waseem Ashraf, Abdulkhaleg Ibrahim, Mahmoud Alhosin, Liliyana Zaayter, Khalid Ouararhni, Christophe Papin, Tanveer Ahmad, Ali Hamiche, Yves Mély, Christian Bronner, Marc Mousli
Cancer is one of the deadliest diseases in the world causing record number of mortalities in both developed and undeveloped countries. Despite a lot of advances and breakthroughs in the field of oncology still, it is very hard to diagnose and treat the cancers at early stages. Here in this review we analyze the potential of Ubiquitin-like containing PHD and Ring Finger domain 1 (UHRF1) as a universal biomarker for cancers. UHRF1 is an important epigenetic regulator maintaining DNA methylation and histone code in the cell...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28834755/zscan4-inhibits-maintenance-dna-methylation-to-facilitate-telomere-elongation-in-mouse-embryonic-stem-cells
#19
Jiameng Dan, Philippe Rousseau, Swanand Hardikar, Nicolas Veland, Jiemin Wong, Chantal Autexier, Taiping Chen
Proper telomere length is essential for embryonic stem cell (ESC) self-renewal and pluripotency. Mouse ESCs (mESCs) sporadically convert to a transient totipotent state similar to that of two-cell (2C) embryos to recover shortened telomeres. Zscan4, which exhibits a burst of expression in 2C-like mESCs, is required for telomere extension in these cells. However, the mechanism by which Zscan4 extends telomeres remains elusive. Here, we show that Zscan4 facilitates telomere elongation by inducing global DNA demethylation through downregulation of Uhrf1 and Dnmt1, major components of the maintenance DNA methylation machinery...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28803780/methylation-of-dna-ligase-1-by-g9a-glp-recruits-uhrf1-to-replicating-dna-and-regulates-dna-methylation
#20
Laure Ferry, Alexandra Fournier, Takeshi Tsusaka, Guillaume Adelmant, Tadahiro Shimazu, Shohei Matano, Olivier Kirsh, Rachel Amouroux, Naoshi Dohmae, Takehiro Suzuki, Guillaume J Filion, Wen Deng, Maud de Dieuleveult, Lauriane Fritsch, Srikanth Kudithipudi, Albert Jeltsch, Heinrich Leonhardt, Petra Hajkova, Jarrod A Marto, Kyohei Arita, Yoichi Shinkai, Pierre-Antoine Defossez
DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1...
August 17, 2017: Molecular Cell
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