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https://www.readbyqxmd.com/read/28433419/disconnect-between-alcohol-induced-alterations-in-chromatin-structure-and-gene-transcription-in-a-mouse-embryonic-stem-cell-model-of-exposure
#1
Kylee J Veazey, Haiqing Wang, Yudhishtar S Bedi, William M Skiles, Richard Cheng-An Chang, Michael C Golding
Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program...
January 11, 2017: Alcohol
https://www.readbyqxmd.com/read/28402695/uhrf2-regulates-local-5-methylcytosine-and-suppresses-spontaneous-seizures
#2
Yidan Liu, Bin Zhang, Xiaoyu Meng, Matthew J Korn, Jack M Parent, Lin-Yu Lu, Xiaochun Yu
The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5 mC levels. Loss of UHRF1 abolishes 5 mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but its biological function is not clear...
April 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28394343/pim1-induces-cellular-senescence-through-phosphorylation-of-uhrf1-at-ser311
#3
J Yang, K Liu, J Yang, B Jin, H Chen, X Zhan, Z Li, L Wang, X Shen, M Li, W Yu, Z Mao
PIM1 is a proto-oncogene, encoding a serine/threonine protein kinase that regulates cell proliferation, survival, differentiation and apoptosis. Previous reports suggest that overexpression of PIM1 can induce cellular senescence. However, the molecular mechanism underlying this process is not fully understood. Here we report that UHRF1 is a novel substrate of PIM1 kinase, which could be phosphorylated at Ser311 and therefore promoted to degradation. Our data demonstrates that PIM1 destabilizes UHRF1, leading to DNA hypomethylation, which consequently results in genomic instability, increased p16 expression and subsequent induction of cellular senescence...
April 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28350187/epigenetic-status-of-h19-igf2-imprinted-genes-and-loss-of-5-hydroxymethylcytosine-in-the-brain-of-cloned-goats
#4
Mingtian Deng, Caifang Ren, Zifei Liu, Guomin Zhang, Feng Wang, Yongjie Wan
In mammals, the imprinted genes play vital roles in development and are generally controlled by DNA methylation at imprinting control regions (ICRs). Recently, it was discovered that 5-hydroxymethylcytosine (5-hmC) is a stable epigenetic modification; however, its functions in cloned animal genomes have not yet been fully elucidated. In this study, we interrogated and quantified the 5-hmC levels in the brain of cloned goats and discovered upregulation of Uhrf1 (p < 0.001), Dnmt1 (p < 0.05), Dnmt3a (p < 0...
March 28, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28334952/dnmt1-mutations-found-in-hsanie-patients-affect-interaction-with-uhrf1-and-neuronal-differentiation
#5
Martha Smets, Stephanie Link, Patricia Wolf, Katrin Schneider, Veronica Solis, Joel Ryan, Daniela Meilinger, Weihua Qin, Heinrich Leonhardt
DNMT1 is recruited to substrate sites by PCNA and UHRF1 to maintain DNA methylation after replication. The cell cycle dependent recruitment of DNMT1 is mediated by the PCNA-binding domain (PBD) and the targeting sequence (TS) within the N-terminal regulatory domain. The TS domain was found to be mutated in patients suffering from hereditary sensory and autonomic neuropathies with dementia and hearing loss (HSANIE) and autosomal dominant cerebellar ataxia deafness and narcolepsy (ADCA-DN) and is associated with global hypomethylation and site specific hypermethylation...
April 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28285359/globular-adiponectin-inhibits-leptin-stimulated-esophageal-adenocarcinoma-cell-proliferation-via-adiponectin-receptor-2-mediated-suppression-of-uhrf1
#6
Jun Wang, Yan Cheng, Xiaoran Yin, Jie Wu, Yumei Luo, Jing Wu, Jia Di, Dong Liu, Yahui Huang, Rong Zhang, Jun Zhang
Esophageal adenocarcinoma (EAC) is one of the most common malignancies in the world which is associated the increased prevalence of obesity. In the context of obesity, leptin can directly contribute to progression of EAC. Adiponectin inhibits leptin-induced oncogenic signaling in EAC cells. However, the exact molecular mechanisms linking obesity, adipokines, and EAC remain far from completely understood. In the present study, we tested the role of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) in adiponectin-induced protective effects against leptin-induced EAC cell proliferation...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28246399/usp7-dependent-histone-h3-deubiquitylation-regulates-maintenance-of-dna-methylation
#7
Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA methylation sites during DNA replication...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28241740/hinokitiol-induces-dna-demethylation-via-dnmt1-and-uhrf1-inhibition-in-colon-cancer-cells
#8
Jung Seon Seo, Young Ha Choi, Ji Wook Moon, Hyeon Soo Kim, Sun-Hwa Park
BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co...
February 27, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28218043/uhrf1-the-key-regulator-of-epigenetics-and-molecular-target-for-cancer-therapeutics
#9
REVIEW
Harsimran Sidhu, Neena Capalash
UHRF1 is a master regulator of epigenome as it coordinates DNA methylation and histone modifications. Compelling evidence suggests a strong link between UHRF1 overexpression and tumorigenesis, substantiating its ability to act as a potential biomarker for cancer diagnosis and prognosis. UHRF1 also mediates repair of damaged DNA that makes cancer cells resistant toward cytocidal drugs. Hence, understanding the molecular mechanism of UHRF1 regulation would help in developing cancer therapeutics. Natural compounds have shown applicability to downregulate UHRF1 leading to growth arrest and apoptosis in cancer cells...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28147265/gender-differences-in-global-but-not-targeted-demethylation-in-ipsc-reprogramming
#10
Inês Milagre, Thomas M Stubbs, Michelle R King, Julia Spindel, Fátima Santos, Felix Krueger, Martin Bachman, Anne Segonds-Pichon, Shankar Balasubramanian, Simon R Andrews, Wendy Dean, Wolf Reik
Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID)-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28128913/overexpression-of-uhrf1-gene-correlates-with-the-major-clinicopathological-parameters-in-urinary-bladder-cancer
#11
Skender Saidi, Zivko Popov, Vesna Janevska, Sasho Panov
INTRODUCTION: Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). OBJECTIVE: The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients' clinical outcome. MATERIALS AND METHODS: In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group...
March 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28112929/dynamics-of-methylated-cytosine-flipping-by-uhrf1
#12
Vasyl Kilin, Krishna Gavvala, Nicolas P F Barthes, Benoît Y Michel, Dongwon Shin, Christian Boudier, Olivier Mauffret, Valeriy Yashchuk, Marc Mousli, Marc Ruff, Florence Granger, Sylvia Eiler, Christian Bronner, Yitzhak Tor, Alain Burger, Yves Mély
DNA methylation patterns, which are critical for gene expression, are replicated by DNA methyltransferase 1 (DNMT1) and ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) proteins. This replication is initiated by the recognition of hemimethylated CpG sites and further flipping of methylated cytosines (mC) by the Set and Ring Associated (SRA) domain of UHRF1. Although crystallography has shed light on the mechanism of mC flipping by SRA, tools are required to monitor in real time how SRA reads DNA and flips the modified nucleobase...
February 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28100769/the-ubiquitin-like-with-phd-and-ring-finger-domains-1-uhrf1-dna-methyltransferase-1-dnmt1-axis-is-a-primary-regulator-of-cell-senescence
#13
Hyun-Jung Jung, Hae-Ok Byun, Byul A Jee, Seongki Min, Un-Woo Jeoun, Young-Kyoung Lee, Yonghak Seo, Hyun Goo Woo, Gyesoon Yoon
As senescence develops, cells sequentially acquire diverse senescent phenotypes along with simultaneous multistage gene reprogramming. It remains unclear what acts as the key regulator of the collective changes in gene expression at initiation of senescent reprogramming. Here we analyzed time series gene expression profiles obtained in two different senescence models in human diploid fibroblasts: replicative senescence and H2O2-induced senescence. Our results demonstrate that suppression of DNA methyltransferase 1 (DNMT1)-mediated DNA methylation activity was an initial event prior to the display of senescent phenotypes...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28060737/elevated-uhrf1-expression-contributes-to-poor-prognosis-by-promoting-cell-proliferation-and-metastasis-in-hepatocellular-carcinoma
#14
Xincheng Liu, Huohui Ou, Leyang Xiang, Xianghong Li, Yu Huang, Dinghua Yang
Ubiquitin-like with plant homeodomain and ring finger domains, 1 (UHRF1) is overexpressed in a variety of tumor tissues and is negatively correlated with prognosis of patients with cancers, yet so far, a comprehensive study of UHRF1 in hepatocellular carcinoma (HCC) has not been conducted. The present study was designed to explore the expression of UHRF1, associated clinical implications, and its possible functions in HCC. Reverse transcription-polymerase chain reaction and immunohistochemical staining were used to detect UHRF1 expression in HCC specimens including cancerous and noncancerous tissues...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059831/effect-of-dihydroartemisinin-on-uhrf1-gene-expression-in-human-prostate-cancer-pc-3-cells
#15
Shijuan Du, Ge Xu, Wenqin Zou, Tingxiu Xiang, Ziguo Luo
As the second most common cancer in men around the world, prostate cancer is increasingly gaining more attention. Dihydroartemisinin (DHA) has been proven to be a promising anticancer agent in vitro as well as in vivo in accumulating data. However, the detailed mechanisms of how DHA action in human prostate cancer PC-3 cells remain elusive. This study aimed to investigate the effects of DHA, a novel anticancer agent, by inhibiting the expression of ubiquitin like containing PHD and ring finger 1 (UHRF1) in PC-3 cells...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27979589/in-vitro-hydroquinone-induced-instauration-of-histone-bivalent-mark-on-human-retroelements-line-1-in-hl60-cells
#16
Monica Mancini, Martina Mandruzzato, Alba C Garzia, Nora Sahnane, Elena Magnani, Filippo Macchi, Mustapha Oulad-Abdelghani, Pierre Oudet, Valentina Bollati, Silvia Fustinoni, Daniela Furlan, Ian M Bonapace
Benzene is extensively used in industry despite its leukemogenic activity, representing a significant occupational hazard. We investigated if long-term treatment with low-doses hydroquinone (HQ), a benzene metabolite, might be sufficient to alter in vitro the epigenetic signature underlining LINE-1 sequences, a poorly explored step in health risks associated with benzene exposure. In HL-60 cell line, exploring the epigenetic events occurring in chromatin, we found the transient instauration of the distinctive signature combining the repressive H3Lys27 tri-methylation mark and the activating H3Lys4 tri-methylation mark (H3K27me3/H3K4me3), indicating a tendency toward a poised chromatin conformation...
December 13, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27958775/distinct-molecular-signature-of-murine-fetal-liver-and-adult-hematopoietic-stem-cells-identify-novel-regulators-of-hematopoietic-stem-cell-function
#17
Javed K Manesia, Monica Franch, Daniel Tabas-Madrid, Ruben Nogales-Cadenas, Thomas Vanwelden, Elisa Van Den Bosch, Zhuofei Xu, Alberto Pascual-Montano, Satish Khurana, Catherine M Verfaillie
During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs...
April 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27956603/uhrf1-controls-the-self-renewal-versus-differentiation-of-hematopoietic-stem-cells-by-epigenetically-regulating-the-cell-division-modes
#18
Jingyao Zhao, Xufeng Chen, Guangrong Song, Jiali Zhang, Haifeng Liu, Xiaolong Liu
Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate. However, how individual HSC makes the decision between self-renewal and differentiation remains largely unknown. Here we report that ablation of the key epigenetic regulator Uhrf1 in the hematopoietic system depletes the HSC pool, leading to hematopoietic failure and lethality. Uhrf1-deficient HSCs display normal survival and proliferation, yet undergo erythroid-biased differentiation at the expense of self-renewal capacity. Notably, Uhrf1 is required for the establishment of DNA methylation patterns of erythroid-specific genes during HSC division...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27923837/the-nci-60-methylome-and-its-integration-into-cellminer
#19
William C Reinhold, Sudhir Varma, Margot Sunshine, Vinodh Rajapakse, Augustin Luna, Kurt W Kohn, Holly Stevenson, Yonghong Wang, Holger Heyn, Vanesa Nogales, Sebastian Moran, David J Goldstein, James H Doroshow, Paul S Meltzer, Manel Esteller, Yves Pommier
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (∼21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and miRNA transcripts, DNA copy number, and protein levels. Here, we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27886214/epigenetic-enhancement-of-the-post-replicative-dna-mismatch-repair-of-mammalian-genomes-by-a-hemi-m-cpg-np95-dnmt1-axis
#20
Keh-Yang Wang, Chun-Chang Chen, Shih-Feng Tsai, Che-Kun James Shen
DNA methylation at C of CpG dyads ((m)CpG) in vertebrate genomes is essential for gene regulation, genome stability and development. We show in this study that proper functioning of post-replicative DNA mismatch repair (MMR) in mammalian cells relies on the presence of genomic (m)CpG, as well as on the maintenance DNA methyltransferase Dnmt1 independently of its catalytic activity. More importantly, high efficiency of mammalian MMR surveillance is achieved through a hemi-(m)CpG-Np95(Uhrf1)-Dnmt1 axis, in which the MMR surveillance complex(es) is recruited to post-replicative DNA by Dnmt1, requiring its interactions with MutSα, as well as with Np95 bound at the hemi-methylated CpG sites...
November 25, 2016: Scientific Reports
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