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Demethylation

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https://www.readbyqxmd.com/read/28318075/thymine-dna-glycosylase-modulates-dna-damage-response-and-gene-expression-by-base-excision-repair-dependent-and-independent-mechanisms
#1
Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa
Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination-induced DNA mismatches, the DNA demethylation process and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here, we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV-induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4(CDT)(2) -mediated ubiquitination that requires a physical interaction between TDG and DNA polymerase clamp PCNA...
March 20, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28318029/computational-study-of-the-reactivity-of-cytosine-derivatives
#2
Jihène Jerbi, Michael Springborg
The aim of the present study is to provide computational insight using dispersion-corrected density-functional calculations into the reactivity properties of modified cytosine in the gas phase and in aqueous solution, whereby special emphasis is put on systems that are obtained through demethylation and methylation. Since this field is relatively incipient, our goal is to identify relationships between reactivity and stability for the modified compounds to understand their biological functionalities. Our results show that addition of a methyl, hydroxylmethyl, formyl, or carboxyl group reduces the length of the nearest hydrogen bond between the cytosine-guanine (CG) base pair and increases the length of the longest hydrogen bond of the DNA base pair...
March 20, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28315794/initiation-of-leaf-somatic-embryogenesis-involves-high-pectin-esterification-auxin-accumulation-and-dna-demethylation-in-quercus-alba
#3
Elena Corredoira, Vanesa Cano, Ivett Bárány, María-Teresa Solís, Héctor Rodríguez, Ana-María Vieitez, María C Risueño, Pilar S Testillano
Somatic embryogenesis is considered a convenient tool for investigating the regulating mechanisms of embryo formation; it is also a feasible system for in vitro regeneration procedures, with many advantages in woody species. Nevertheless, trees have shown recalcitrance to somatic embryogenesis, and its efficiency remains very low in many cases. Consequently, despite the clear potential of somatic embryogenesis in tree breeding programs, its application is limited since factors responsible for embryogenesis initiation have not yet been completely elucidated...
March 1, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28314512/modulation-of-opioid-receptor-affinity-and-efficacy-via-n-substitution-of-9%C3%AE-hydroxy-5-3-hydroxyphenyl-morphan-synthesis-and-computer-simulation-study
#4
Phong M Truong, Sergio A Hassan, Yong-Sok Lee, Theresa A Kopajtic, Jonathan L Katz, Aaron M Chadderdon, John R Traynor, Jeffrey R Deschamps, Arthur E Jacobson, Kenner C Rice
The enantiomers of a variety of N-alkyl-, N-aralkyl-, and N-cyclopropylalkyl-9β-hydroxy-5-(3-hydroxyphenyl)morphans were synthesized employing cyanogen bromide and K2CO3 to improve the original N-demethylation procedure. Their binding affinity to the μ-, δ-, and κ-opioid receptors (ORs) was determined and functional (GTPγ(35)S) assays were carried out on those with reasonable affinity. The 1R,5R,9S-enantiomers (1R,5R,9S)-(-)-5-(3-hydroxyphenyl)-2-(4-nitrophenethyl)-2-azabicyclo[3.3.1]nonan-9-ol (1R,5R,9S-16), (1R,5R,9S)-(-) 2-cinnamyl-5-(3-hydroxyphenyl)-2-azabicyclo[3...
March 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28302794/dna-sequence-dependent-epigenetic-inheritance-of-gene-silencing-and-histone-h3k9-methylation
#5
Xiaoyi Wang, Danesh Moazed
Epigenetic inheritance mechanisms play fundamental roles in maintaining cellular memory of gene expression states. In fission yeast, histone H3 lysine 9 (H3K9me) is methylated at heterochromatic domains. These domains can be epigenetically inherited when epi1+, encoding an enzyme that promotes H3K9 demethylation, is deleted. How native epigenetic states are stably maintained in epe1(+) cells remains unknown. Here, we developed a system to examine the role of DNA sequence and genomic context in propagation of a cis-heritable H3K9me-dependent silenced state...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28302141/dna-hypomethylation-and-aberrant-expression-of-the-human-endogenous-retrovirus-ervwe1-syncytin-1-in-seminomas
#6
Martina Benešová, Kateřina Trejbalová, Denisa Kovářová, Zdenka Vernerová, Tomáš Hron, Dana Kučerová, Jiří Hejnar
BACKGROUND: Syncytin-1 and 2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. Previously, we have shown that the transcriptional suppression of ERVWE1 promoter is controlled epigenetically by DNA methylation and chromatin modifications...
March 17, 2017: Retrovirology
https://www.readbyqxmd.com/read/28301293/signatures-of-dna-target-selectivity-by-ets-transcription-factors
#7
Gregory M K Poon, Hye Mi Kim
The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation...
March 16, 2017: Transcription
https://www.readbyqxmd.com/read/28298929/%C3%AE-arrestin1-mir-326-transcription-unit-is-epigenetically-regulated-in-neural-stem-cells-where-it-controls-stemness-and-growth-arrest
#8
Agnese Po, Federica Begalli, Luana Abballe, Vincenzo Alfano, Zein Mersini Besharat, Giuseppina Catanzaro, Alessandra Vacca, Maddalena Napolitano, Marco Tafani, Felice Giangaspero, Franco Locatelli, Elisabetta Ferretti, Evelina Miele
Cell development is regulated by a complex network of mRNA-encoded proteins and microRNAs, all funnelling onto the modulation of self-renewal or differentiation genes. How intragenic microRNAs and their host genes are transcriptionally coregulated and their functional relationships for the control of neural stem cells (NSCs) are poorly understood. We propose here the intragenic miR-326 and its host gene β-arrestin1 as novel players whose epigenetic silencing maintains stemness in normal cerebellar stem cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28296931/helios-expression-and-foxp3-tsdr-methylation-of-ifny-and-ifny-treg-from-kidney-transplant-recipients-with-good-long-term-graft-function
#9
Karina Trojan, Christian Unterrainer, Rolf Weimer, Nuray Bulut, Christian Morath, Mostafa Aly, Li Zhu, Gerhard Opelz, Volker Daniel
BACKGROUND: There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient. METHOD: Helios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR) served as indicators for stability of Foxp3 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28296334/a-study-on-cyp2c19-and-cyp2d6-polymorphic-effects-on-pharmacokinetics-and-pharmacodynamics-of-amitriptyline-in-healthy-koreans
#10
S Ryu, S Park, J H Lee, Y R Kim, H S Na, H S Lim, H Y Choi, I Y Hwang, J G Lee, Z W Park, W Y Oh, J M Kim, S E Choi
We performed a double-blinded, genotype-based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty-four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N-demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19...
March 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28294608/an-engineered-split-tet2-enzyme-for-inducible-epigenetic-remodeling
#11
Minjung Lee, Jia Li, Yi Liang, Guolin Ma, Jixiang Zhang, Lian He, Yuliang Liu, Qian Li, Minyong Li, Deqiang Sun, Yubin Zhou, Yun Huang
The Ten-eleven translocation (TET) family of 5-methylcytosine (5mC) dioxygenases catalyze the conversion of 5mC into 5-hydroxymethylcytosine (5hmC) and further oxidized species to promote active DNA demethylation. Here we engineered a split-TET2 enzyme to enable temporal control of 5mC oxidation and subsequent remodeling of epigenetic states in mammalian cells. We further demonstrate the use of this chemically-inducible system to dissect the correlation between DNA hydroxymethylation and chromatin accessibility in the mammalian genome...
March 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28294107/antifungal-mechanisms-of-zno-and-ag-nanoparticles-to-sclerotinia-homoeocarpa
#12
Junli Li, Hyunkyu Sang, Huiyuan Guo, James T Popko, Lili He, Jason C White, Om Parkash Dhankher, Geunhwa Jung, Baoshan Xing
Fungicides have extensively been used to effectively combat fungal diseases on a range of plant species, but resistance to multiple active ingredients has developed in pathogens such as Sclerotinia homoeocarpa, the causal agent of dollar spot on cool-season turfgrasses. Recently, ZnO and Ag nanoparticles (NPs) have received increased attention due to their antimicrobial activities. In this study, the NPs' toxicity and mechanisms of action were investigated as alternative antifungal agents against S. homoeocarpa isolates that varied in their resistance to demethylation inhibitor (DMI) fungicides...
April 18, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28293326/line-1-is-preferentially-hypomethylated-within-adenomatous-polyps-in-the-presence-of-synchronous-colorectal-cancer
#13
Alice Chu Jiang, Lela Buckingham, William Barbanera, Amoah Yeboah Korang, Faraz Bishesari, Joshua Melson
BACKGROUND: Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Whether features of adenomas could serve as predictors of synchronous CRC is not known. Here, we investigate whether global methylation markers, including LINE-1, differ within adenomas in patients with and without synchronous CRC. METHODS: Colorectal tubular/tubulovillous adenomatous polyps in the absence (P group, n = 45) and in the presence of synchronous CRC (PC group, n = 32) were identified...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28290706/the-metabolism-of-berberine-and-its-contribution-to-the-pharmacological-effects
#14
Kun Wang, Xinchi Feng, Liwei Chai, Shijie Cao, Feng Qiu
Berberine, a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including antimicrobial, anti-diabetic, anti-cancer activities. Meanwhile, berberine undergoes extensive metabolism after oral administration which results in its extremely low plasma exposure. Therefore, it is believed that the metabolites of berberine also contribute a lot to its pharmacological effects. Along these lines, this review covers the metabolism studies of berberine in terms of its metabolic pathways and metabolic organs based on the identified metabolites, and it also covers the pharmacological activities of its active metabolites...
March 14, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28289705/als-patients-regulatory-t-lymphocytes-are-dysfunctional-and-correlate-with-disease-progression-rate-and-severity
#15
David R Beers, Weihua Zhao, Jinghong Wang, Xiujun Zhang, Shixiang Wen, Dan Neal, Jason R Thonhoff, Abdullah S Alsuliman, Elizabeth J Shpall, Katy Rezvani, Stanley H Appel
Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288000/age-associated-chromatin-relaxation-is-enhanced-in-huntington-s-disease-mice
#16
Myungsun Park, Byungkuk Min, Kyuheum Jeon, Sunwha Cho, Jung Sun Park, Jisun Kim, Jeha Jeon, Jinhoi Song, Seokho Kim, Sangkyun Jeong, Hyemyung Seo, Yong-Kook Kang
Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PCRseq-based method to examine expression profile of 395 exonic segments from 260 "epi-driver" genes in splenic T lymphocytes from aged HD mice. We identified 67 exonic segments differentially expressed between young and aged HD mice, most of them upregulated in the aged...
March 12, 2017: Aging
https://www.readbyqxmd.com/read/28284938/human-il-6r-hi-tigit-cd4-cd127-low-cd25-t-cells-display-potent-in-vitro-suppressive-capacity-and-a-distinct-th17-profile
#17
Ricardo C Ferreira, Daniel B Rainbow, Arcadio Rubio García, Marcin L Pekalski, Linsey Porter, João J Oliveira, Frank Waldron-Lynch, Linda S Wicker, John A Todd
To date many clinical studies aim to increase the number and/or fitness of CD4(+)CD127(low)CD25(+) regulatory T cells (Tregs) in vivo to harness their regulatory potential in the context of treating autoimmune disease. Here, we sought to define the phenotype and function of Tregs expressing the highest levels of IL-6R. We have identified a population of CD4(+)CD127(low)CD25(+) TIGIT(-) T cells distinguished by their elevated IL-6R expression that lacked expression of HELIOS, showed higher CTLA-4 expression, and displayed increased suppressive capacity compared to IL-6R(hi)TIGIT(+) Tregs...
March 8, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#18
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28279976/regulation-of-hypoxia-responses-by-flavin-adenine-dinucleotide-dependent-modulation-of-hif-1%C3%AE-protein-stability
#19
Suk-Jin Yang, Young Soo Park, Jung Hee Cho, Byul Moon, Hyun-Jung Ahn, Ju Yeon Lee, Zhi Xie, Yuli Wang, David Pocalyko, Dong Chul Lee, Hyun Ahm Sohn, Minho Kang, Jin Young Kim, Eunhee Kim, Kyung Chan Park, Jung-Ae Kim, Young Il Yeom
Oxygen deprivation induces a range of cellular adaptive responses that enable to drive cancer progression. Here, we report that lysine-specific demethylase 1 (LSD1) upregulates hypoxia responses by demethylating RACK1 protein, a component of hypoxia-inducible factor (HIF) ubiquitination machinery, and consequently suppressing the oxygen-independent degradation of HIF-1α. This ability of LSD1 is attenuated during prolonged hypoxia, with a decrease in the cellular level of flavin adenine dinucleotide (FAD), a metabolic cofactor of LSD1, causing HIF-1α downregulation in later stages of hypoxia...
March 9, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28279930/metabolites-identification-of-berberine-in-rats-using-ultra-high-performance-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry
#20
Kun Wang, Liwei Chai, Xinchi Feng, Zhongbo Liu, Hongxia Liu, Liqin Ding, Feng Qiu
Berberine (BBR), the principle component for many medicinal plants such as Coptis chinensis Franch., Phellodendron chinense Schneid., and Mahonia bealei (Fort.) Carr., possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic and antidiabetic activities. In this study, a rapid and reliable method using a five-step strategy based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), and metabolynx™ software with mass defect filter (MDF) technique was developed to investigate the metabolism of BBR...
February 27, 2017: Journal of Pharmaceutical and Biomedical Analysis
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