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https://www.readbyqxmd.com/read/29323674/can-5-methylcytosine-analogues-with-extended-alkyl-side-chains-guide-dna-methylation
#1
D Kotandeniya, C L Seiler, J Fernandez, S S Pujari, L Curwick, K Murphy, S Wickramaratne, S Yan, D Murphy, Yuk Y Sham, N Y Tretyakova
5-Methylcytosine (MeC) is an endogenous modification of DNA that plays a crucial role in DNA-protein interactions, chromatin structure, epigenetic regulation, and DNA repair. MeC is produced via enzymatic methylation of the C-5 position of cytosine by DNA-methyltransferases (DNMT) which use S-adenosylmethionine (SAM) as a cofactor. Hemimethylated CG dinucleotides generated as a result of DNA replication are specifically recognized and methylated by maintenance DNA methyltransferase 1 (DNMT1). The accuracy of DNMT1-mediated methylation is essential for preserving tissue-specific DNA methylation and thus gene expression patterns...
January 11, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29313974/genetic-variants-in-rora-and-dnmt1-associated-with-cutaneous-melanoma-survival
#2
Bo Li, Yanru Wang, Yinghui Xu, Hongliang Liu, Wendy Bloomer, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Xin Li, Jiali Han, Qingyi Wei
Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29297981/primary-biliary-cholangitis-in-british-columbia-first-nations-clinical-features-and-discovery-of-novel-genetic-susceptibility-loci
#3
Sirisha Asuri, Sarah McIntosh, Valerie Taylor, Andrew Rokeby, James Kelly, Karey Shumansky, L Leigh Field, Eric M Yoshida, Laura Arbour
BACKGROUND AND AIMS: Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by destruction of intrahepatic bile ducts, portal inflammation, and cirrhosis. Although rare in most populations, it is prevalent and often familial in British Columbia First Nations. We hypothesized that major genetic factors increased the risk in First Nations. METHODS: 44 individuals with PBC and 61 unaffected relatives from 32 First Nations families participated...
January 3, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29295997/diabetes-impairs-wound-healing-by-dnmt1-dependent-dysregulation-of-hematopoietic-stem-cells-differentiation-towards-macrophages
#4
Jinglian Yan, Guodong Tie, Shouying Wang, Amanda Tutto, Natale DeMarco, Lyne Khair, Thomas G Fazzio, Louis M Messina
People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29281720/reversible-dual-inhibitor-against-g9a-and-dnmt1-improves-human-ipsc-derivation-enhancing-met-and-facilitating-transcription-factor-engagement-to-the-genome
#5
Juan Roberto Rodriguez-Madoz, Edurne San Jose-Eneriz, Obdulia Rabal, Natalia Zapata-Linares, Estibaliz Miranda, Saray Rodriguez, Angelo Porciuncula, Amaia Vilas-Zornoza, Leire Garate, Victor Segura, Elizabeth Guruceaga, Xabier Agirre, Julen Oyarzabal, Felipe Prosper
The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods...
2017: PloS One
https://www.readbyqxmd.com/read/29274743/ankrd11-associated-with-intellectual-disability-and-autism-regulates-dendrite-differentiation-via-the-bdnf-trkb-signaling-pathway
#6
Minhan Ka, Woo-Yang Kim
Haploinsufficiency of ANKRD11 due to deletion or truncation mutations causes KBG syndrome, a rare genetic disorder characterized by intellectual disability, autism spectrum disorder, and craniofacial abnormalities. However, little is known about the neurobiological role of ANKRD11 during brain development. Here we show that ANKRD11 regulates pyramidal neuron migration and dendritic differentiation in the developing moue cerebral cortex. Using an in utero manipulation approach, we found that Ankrd11 knockdown delayed radial migration of cortical neurons...
December 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29262320/the-arginine-methyltransferase-prmt6-regulates-dna-methylation-and-contributes-to-global-dna-hypomethylation-in-cancer
#7
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/29261844/crosstalk-between-histone-and-dna-methylation-in-regulation-of-retinal-matrix-metalloproteinase-9-in-diabetes
#8
Arul J Duraisamy, Manish Mishra, Renu A Kowluru
Purpose: Diabetes activates matrix metalloproteinase-9 (MMP-9), and MMP-9 via damaging retinal mitochondria, activates capillary cell apoptosis. MMP-9 promoter has binding sites for many transcription factors, and in diabetes its promoter undergoes epigenetic modifications, including histone modifications and DNA methylation. Enhancer of Zeste homolog 2 (Ezh2), which catalyzes dimethylation/trimethylation of histone 3 lysine 27 (H3K27me2 and me3), is also associated with DNA methylation...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29260742/-overexpression-of-dna-methyltransferases-in-persistency-of-cccdna-pool-in-chronic-hepatitis-b
#9
D S Kostyushev, A P Zueva, S A Brezgin, A D Lipatnikov, V N Simirskii, D Glebe, E V Volchkova, G A Shipulin, V P Chulanov
AIM: To define the role of DNA-methyltransferases of type 1 and type 3A in hepatitis B viral cycle. MATERIAL AND METHODS: Human hepatoma cells HepG2 with stable expression of 1.1-mer HBV genome were transfected with vectors encoding DNA-methyltransferase 1 (DNMT1), DNA-methyltransferase 3A (DNMT3A) or were co-transfected with these vectors. Total HBV DNA copy number, relative expression of pregenomic RNA (pgRNA), S-protein-encoding RNA (S-RNA) and cccDNA were analyzed by quantitative and semi-quantitative real-time PCR-analysis with TaqMan probes for assessment of DNMTs-mediated effects on HBV...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29259247/ras-pathway-mutation-patterns-define-epigenetic-subclasses-in-juvenile-myelomonocytic-leukemia
#10
Daniel B Lipka, Tania Witte, Reka Toth, Jing Yang, Manuel Wiesenfarth, Peter Nöllke, Alexandra Fischer, David Brocks, Zuguang Gu, Jeongbin Park, Brigitte Strahm, Marcin Wlodarski, Ayami Yoshimi, Rainer Claus, Michael Lübbert, Hauke Busch, Melanie Boerries, Mark Hartmann, Maximilian Schönung, Umut Kilik, Jens Langstein, Justyna A Wierzbinska, Caroline Pabst, Swati Garg, Albert Catalá, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Franco Locatelli, Riccardo Masetti, Markus Schmugge, Owen Smith, Jan Stary, Marek Ussowicz, Marry M van den Heuvel-Eibrink, Yassen Assenov, Matthias Schlesner, Charlotte Niemeyer, Christian Flotho, Christoph Plass
Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29247843/dietary-betaine-supplementation-in-hens-modulates-hypothalamic-expression-of-cholesterol-metabolic-genes-in-f1-cockerels-through-modification-of-dna-methylation
#11
Abdulrahman A Idriss, Yun Hu, Zhen Hou, Yan Hu, Qinwei Sun, Nagmeldin A Omer, Halima Abobaker, Yingdong Ni, Ruqian Zhao
Betaine is widely used in animal nutrition to promote growth, development and methyl donor during methionine metabolism through nutritional reprogramming via regulation of gene expression. Prenatal betaine exposure is reported to modulate hypothalamic cholesterol metabolism in chickens, yet it remains unknown whether feeding hens with betaine-supplemented diet may affect hypothalamic cholesterol metabolism in F1 offspring. In this study, hens were fed with basal or betaine-supplemented (0.5%) for 30days, and the eggs were collected for incubation...
December 14, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29247823/the-long-noncoding-rna-lucat1-promotes-tumorigenesis-by-controlling-ubiquitination-and-stability-of-dna-methyltransferase-1-in-esophageal-squamous-cell-carcinoma
#12
Jung-Ho Yoon, Bo-Hyun You, Chan Hyuk Park, Yeong Jin Kim, Jin-Wu Nam, Sang Kil Lee
Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells...
December 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29236331/reduction-of-histone-marks-h3k9me3-and-h3k27me3-by-epidrug-induces-neuroendocrine-differentiation-in-prostate-cancer
#13
Eunsohl Lee, Jingcheng Wang, Younghun Jung, Frank C Cackowski, Russell S Taichman
Neuroendocrine prostate cancer (NE PCa) is an aggressive malignancy, often presenting with advanced metastasis. We previously reported that reduction of histone marks regulated by DNMT1 following epidrug (5-Azacitidine, 5-Aza) treatment controls induction of epithelial to mesenchymal (EMT) and a cancer stem cell (CSC) phenotype, which facilitates tumorigenesis in PCa cells. Here, we use the epidrug 5-Aza as a model for how histone marks may regulate the reprogramming of prostate adenocarcinoma into NE phenotypic cells...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29234621/neonatal-exposure-to-6-n-propyl-thiouracil-an-anti-thyroid-drug-alters-expression-of-hepatic-dna-methyltransferases-methyl-cpg-binding-proteins-gadd45a-p53-and-pcna-in-adult-male-rats
#14
Suresh Kumar Bunker, Jagneshwar Dandapat, Gagan B N Chainy, Sunil Kumar Sahoo, Prabhat Kumar Nayak
Background: Neonatal 6-n-propyl-2-thiouracil (PTU) exposure to male rats is reported to impair liver function in adulthood. However, the mechanism by which the drug impairs liver function is not well known. Objectives: The objectives of the study were to investigate the effects of neonatal exposure of PTU on the expression of DNA methyltransferases (DNMTs), methyl-DNA binding proteins (MBDs), Gadd45a, p53, and proliferating cell nuclear antigen (PCNA) in adult rat liver...
November 2017: European Thyroid Journal
https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#15
Wenji Li, Zheng-Yuan Su, Yue Guo, Chengyue Zhang, RenYi Wu, Linbo Gao, Xi Zheng, Zhi-Yun Du, Kun Zhang, Ah-Ng Kong
The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydrothiopyran-4-one (F10) and (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways...
December 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29228563/riluzole-a-potential-therapeutic-intervention-in-human-brain-tumor-stem-like-cells
#16
Swetlana Sperling, Thiha Aung, Sabine Martin, Veit Rohde, Milena Ninkovic
A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29223407/stat3-mediated-epigenetic-silencing-of-foxp3-in-lada-t-cells-is-regulated-through-hdac5-and-dnmt1
#17
Can Hou, Yanjun Zhong, Zhen Wang, Zhao Ming, Gan Huang, Lin Ouyang, Yijun Li, Qianjin Lu, Zhiguang Zhou
In LADA patients, Tregs are reduced and FOXP3 is downregulated in CD4+ T cells, but the etiology remains unclear. Our study included in 20 LADA patients and 20 healthy control patients. qRT-PCR results showed that STAT3, HDAC3, HDAC5, SIRT1, DNMT1 and DNMT3b mRNAs were significantly upregulated in LADA CD4+ T cells than controls, while FOXP3 mRNA significantly decreased. p-STAT3, STAT3, DNMT1 and DNMT3b expressions were increased demonstrated by western blot. ChIP-PCR suggested that p-STAT3 binds to the Foxp3 promoter, meanwhile, histone H3 acetylation at K9 and K14 of FOXP3 promoter were significantly lower than controls...
December 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29221985/hotair-mediated-reciprocal-regulation-of-ezh2-and-dnmt1-contribute-to-polyphyllin-i-inhibited-growth-of-castration-resistant-prostate-cancer-cells-in-vitro-and-in-vivo
#18
SongTao Xiang, PeiLiang Zou, Qing Tang, Fang Zheng, JingJing Wu, ZhiQiang Chen, Swei Sunny Hann
BACKGROUND: Polyphyllin I (PPI), one of the steroidal saponins in paris polyphylla, has been reported to exhibit antitumor effects. However, the detailed molecular mechanism underlying this has not been elucidated. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Flow cytometry assays, respectively. Cell invasion and migration were examined by Transwell invasion and wound healing assays...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29221215/dnmt1-overexpression-predicting-gastric-carcinogenesis-subsequent-progression-and-prognosis-a-meta-and-bioinformatic-analysis
#19
Tianmiao Ma, Hao Li, Mingjun Sun, Yuan Yuan, Li-Ping Sun
DNMT1 is important in maintaining DNA methylation, and participates in the oncogenesis via up- or down-regulation leading to hyper-methylation or hypo-methylation. In the meta and bioinformatic analysis, we found that DNMT1 expression was higher in gastric cancer, compared with normal (p < 0.00001), para-cancerous (p = 0.0004) and dysplasia (p < 0.00001) tissues. DNMT1 up-regulation was associated with gender (OR = 2.27, p = 0.006), differentiation (OR = 0.21, p = 0.01) and TNM stage (OR = 0.31, p = 0...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221147/long-noncoding-rna-linc00673-epigenetically-suppresses-klf4-by-interacting-with-ezh2-and-dnmt1-in-gastric-cancer
#20
Ming-Chen Ba, Hui Long, Shu-Zhong Cui, Yuan-Feng Gong, Zhao-Fei Yan, Yin-Bing Wu, Yi-Nuo Tu
Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients...
November 10, 2017: Oncotarget
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