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https://www.readbyqxmd.com/read/29898922/epigenetic-alterations-mediate-ipsc-normalization-of-dna-repair-expression-and-tnr-stability-in-huntington-s-disease
#1
Peter A Mollica, Martina Zamponi, John A Reid, Deepak K Sharma, Alyson E White, Roy C Ogle, Robert D Bruno, Patrick C Sachs
Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat (TNR) expansion within the HTT gene. The mechanisms underlying HD-associated cellular dysfunction during pluripotency and neurodevelopment, are poorly understood. Here we tested the hypothesis that hypomethylation during cellular reprogramming leads to up-regulation of DNA repair genes and stabilization of TNRs in HD cells. We sought to determine how the HD TNR region is affected by global epigenetic changes through cellular reprogramming and early neurodifferentiation...
June 13, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29862069/effects-of-5-hydroxymethylcytosine-epigenetic-modification-on-the-stability-and-molecular-recognition-of-vegf-i-motif-and-g-quadruplex-structures
#2
Rhianna K Morgan, Michael M Molnar, Harshul Batra, Bethany Summerford, Randy M Wadkins, Tracy A Brooks
Promoters often contain asymmetric G- and C-rich strands, in which the cytosines are prone to epigenetic modification via methylation (5-mC) and 5-hydroxymethylation (5-hmC). These sequences can also form four-stranded G-quadruplex (G4) or i-motif (iM) secondary structures. Although the requisite sequences for epigenetic modulation and iM/G4 formation are similar and can overlap, they are unlikely to coexist. Despite 5-hmC being an oxidization product of 5-mC, the two modified bases cluster at distinct loci...
2018: Journal of Nucleic Acids
https://www.readbyqxmd.com/read/29858571/tet1-and-tet2-maintain-mesenchymal-stem-cell-homeostasis-via-demethylation-of-the-p2rx7-promoter
#3
Ruili Yang, Tingting Yu, Xiaoxing Kou, Xiang Gao, Chider Chen, Dawei Liu, Yanheng Zhou, Songtao Shi
Ten-eleven translocation (Tet) family-mediated DNA oxidation represents an epigenetic modification capable of converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), which regulates various biological processes. However, it is unknown whether Tet family affects mesenchymal stem cells (MSCs) or the skeletal system. Here we show that depletion of Tet1 and Tet2 results in impaired self-renewal and differentiation of bone marrow MSCs (BMMSCs) and a significant osteopenia phenotype. Tet1 and Tet2 deficiency reduces demethylation of the P2rX7 promoter and downregulates exosome release, leading to intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p...
June 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29850477/the-progress-of-methylation-regulation-in-gene-expression-of-cervical-cancer
#4
REVIEW
Chunyang Feng, Junxue Dong, Weiqin Chang, Manhua Cui, Tianmin Xu
Cervical cancer is one of the most common gynecological tumors in females, which is closely related to high-rate HPV infection. Methylation alteration is a type of epigenetic decoration that regulates the expression of genes without changing the DNA sequence, and it is essential for the progression of cervical cancer in pathogenesis while reflecting the prognosis and therapeutic sensitivity in clinical practice. Hydroxymethylation has been discovered in recent years, thus making 5-hmC, the more stable marker, attract more attention in the field of methylation research...
2018: International Journal of Genomics
https://www.readbyqxmd.com/read/29803640/loss-of-5-hydroxymethylcytosine-is-an-epigenetic-biomarker-in-cutaneous-t-cell-lymphoma
#5
Lei Qiu, Fengjie Liu, Shengguo Yi, Xueying Li, Xiaoqing Liu, Cheng Xiao, Christine Guo Lian, Ping Tu, Yang Wang
DNA hydroxymethylation at the 5 position of cytosine (5-hmC) is a product of the ten-eleven translocation (TET) family of DNA hydroxylases. Accumulating evidence shows that loss of 5-hmC is critical for various biological and pathological processes. However, its level in cutaneous T cell lymphoma remains largely unknown. Here we report that the loss of 5-hmC is an epigenetic hallmark of cutaneous T cell lymphoma (CTCL), with diagnostic and prognostic implications. Immunohistochemistry staining on 90 mycosis fungoides (MF) cases demonstrated a significant decrease of 5-hmC staining in CD4+ T cells in patch and tumor stages, especially in MF-LCT, compared to benign inflammatory dermatoses...
May 24, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29797259/genome-wide-mapping-of-methylated-and-hydroxyl-methylated-cytosines-using-a-modified-hpaii-tiny-fragment-enrichment-by-ligation-mediated-pcr-tagged-sequencing-protocol
#6
Sanchari Battachariyya, Ruslana Tytarenko, Christoph Heuck, John Greally, Amit Verma
Here we describe a method for genome wide investigation of methylation and hydroxymethylation status of cytosines. This protocol is an improvement of the HELP-tagging protocol previously described by Suzuki et al. It involves the glucosylation of 5-hydroxymethylcytosines (5-hmC) with β-glucosyl transferase (β-GT), thus rendering them resistant to digestion by MspI. Parallel digestion of β-GT treated samples with MspI, untreated sample with MspI and another untreated sample with HpaII, followed by adapter ligation, parallel sequencing and bioinformatics processing results in a differential display of MspI digestion sites that allows the determination of the distribution of 5-methylcytosines (5-mC) and 5-hmC at these sites...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29772230/replacing-c189-in-the-bzip-domain-of-zta-with-s-t-v-or-a-changes-dna-binding-specificity-to-four-types-of-double-stranded-dna
#7
Sreejana Ray, Desiree Tillo, Nima Assad, Aniekanabasi Ufot, Christopher Deppmann, Stewart R Durell, Aleksey Porollo, Charles Vinson
Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29629447/electrochemical-signal-amplified-detection-of-5-methylcytosine-and-5-hydroxymethylcytosine-in-dna-using-glucose-modification-coupled-with-restriction-endonucleases
#8
Yin Yang, Guoqing Yang, Hongfei Chen, Hui Zhang, Jiu-Ju Feng, Chenxin Cai
The levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in DNA (5-mC-DNA and 5-hmC-DNA) are strongly correlated with cancer occurrence and development. The ability to distinguish and quantitatively detect them is important for cancer research. We have developed a hybridization chain reaction (HCR)-based electrochemical assay for the signal-amplified detection of the relative contents of 5-mC-DNA and 5-hmC-DNA. The DNA duplexes (containing 5-mC-DNA and 5-hmC-DNA with different percentages) were modified on a gold electrode...
April 30, 2018: Analyst
https://www.readbyqxmd.com/read/29549908/ten-eleven-translocation-1-tet1-gene-is-a-potential-target-of-mir-21-5p-in-human-colorectal-cancer
#9
Ya-Wen Cheng, Chia-Jung Chou, Pei-Ming Yang
DNA 5-methylcytosine (5-mC) methylation, a key epigenetic mark, is critical for biological and pathological processes. Aberrant DNA methylation occurs in all tumor types and correlates with tumor suppressor gene silencing. DNA methylation is thought to be very stable, and active DNA demethylation remains a long-standing enigma. Recently, the ten-eleven translocation (TET) family of oxygenases are found to oxidize 5-mC to 5-hydroxymethylcytosine (5-hmC), which is prerequisite for active DNA demethylation. Both TET1 expression and global 5-hmC content are significantly reduced in colorectal cancer (CRC), the top leading cause of cancer-related death in the world...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29545476/d-2-hydroxyglutarate-is-necessary-and-sufficient-for-isocitrate-dehydrogenase-1-mutant-induced-mir148a-promoter-methylation
#10
Tie Li, Christopher D Cox, Byram H Ozer, Nhung T Nguyen, HuyTram N Nguyen, Thomas J Lai, Sichen Li, Fei Liu, Harley I Kornblum, Linda M Liau, Phioanh L Nghiemphu, Timothy F Cloughesy, Albert Lai
Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG-dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant-associated glioma CpG island methylator phenotype (G-CIMP) and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of MIR148A and other G-CIMP promoters remains to be elucidated...
March 15, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29542811/ten-eleven-translocation-2-regulates-dna-hydroxymethylation-status-and-psoriasiform-dermatitis-progression-in-mice
#11
Xin Wang, Xinxin Liu, Xiaoru Duan, Ke Zhu, Song Zhang, Lu Gan, Nian Liu, Himanshu Jaypaul, Johanna T Makamure, Zhangyin Ming, Hongxiang Chen
Epigenetics plays an important role in the development and progression of many diseases. There is increasing evidence for the importance of epigenetic modifications in the progression of psoriasis. The aim of this study was to examine the role and potential mechanism of action of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation-2 (TET2) in psoriasiform dermatitis in mice. Immunohistochemical staining was performed on psoriasis patients and healthy controls. Topical application of imiquimod cream to the dorsal skin of mice was used to induce psoriasiform dermatitis...
March 15, 2018: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29491831/species-specific-5-mc-and-5-hmc-genomic-landscapes-indicate-epigenetic-contribution-to-human-brain-evolution
#12
Andy Madrid, Pankaj Chopra, Reid S Alisch
Human evolution from non-human primates has seen substantial change in the central nervous system, with the molecular mechanisms underlying human brain evolution remaining largely unknown. Methylation of cytosine at the fifth carbon (5-methylcytosine; 5 mC) is an essential epigenetic mark linked to neurodevelopment, as well as neurological disease. The emergence of another modified form of cytosine (5-hydroxymethylcytosine; 5 hmC) that is enriched in the brain further substantiates a role for these epigenetic marks in neurodevelopment, yet little is known about the evolutionary importance of these marks in brain development...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29478287/altered-epigenetic-pathways-and-cell-cycle-dysregulation-in-healthy-appearing-skin-of-patients-with-koebnerized-squamous-cell-carcinomas-following-skin-surgery
#13
T Gambichler, I Rüddel, S Hessam, F G Bechara, E Stockfleth, L Schmitz
BACKGROUND: Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event. OBJECTIVES: To study molecular pathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal. METHODS: We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs...
February 25, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29428949/elevated-global-dna-methylation-is-not-exclusive-to-amyotrophic-lateral-sclerosis-and-is-also-observed-in-spinocerebellar-ataxia-types-1-and-2
#14
Hamid Hamzeiy, Doruk Savaş, Ceren Tunca, Nesli Ece Şen, Aslı Gündoğdu Eken, Irmak Şahbaz, Daniela Calini, Cinzia Tiloca, Nicola Ticozzi, Antonia Ratti, Vincenzo Silani, A Nazlı Başak
Adult-onset neurological disorders are caused and influenced by a multitude of different factors, including epigenetic modifications. Here, using an ELISA kit selected upon careful testing, we investigated global 5-methylcytosine (5-mC) levels in sporadic and familial amyotrophic lateral sclerosis (sALS and fALS), spinocerebellar ataxia types 1 and 2 (SCA1 and SCA2), Huntington's disease, Friedreich's ataxia, and myotonic dystrophy type 1. We report a significant elevation in global 5-mC levels of about 2-7% on average for sALS (p < 0...
2018: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/29427306/impaired-fear-extinction-in-serotonin-transporter-knockout-rats-is-associated-with-increased-5-hydroxymethylcytosine-in-the-amygdala
#15
Ling Shan, Hang-Yuan Guo, Corina N A M van den Heuvel, Joop van Heerikhuize, Judith R Homberg
AIMS: One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA methylation/demethylation is crucial for fear extinction in these brain areas and is associated with neuronal activation marker c-Fos expression. We hypothesized that impaired fear extinction in serotonin transporter knockout (5-HTT-/- ) rats is related to changes in DNA (de) methylation and c-Fos expression in the prefrontal cortex (PFC) and/or amygdala...
February 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29410709/genomic-5-mc-contents-in-peripheral-blood-leukocytes-were-independent-protective-factors-for-coronary-artery-disease-with-a-specific-profile-in-different-leukocyte-subtypes
#16
Qianyun Deng, Wei Huang, Chunyan Peng, Jiajia Gao, Zuhua Li, Xueping Qiu, Na Yang, Bifeng Yuan, Fang Zheng
Background: Alterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blood cell subtypes of coronary artery disease (CAD) patients are still inconclusive, and much less is known about mechanisms underlying. Results: We recruited 265 CAD patients and 270 healthy controls with genomic DNA from PBLs, of which 50 patients and 50 controls were randomly chosen with DNA from isolated neutrophils, lymphocytes and monocytes, and RNA from PBLs...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29407727/dna-redox-modulations-and-global-dna-methylation-in-bipolar-disorder-effects-of-sex-smoking-and-illness-state
#17
Deniz Ceylan, Gustavo Scola, Zeliha Tunca, Cameron Isaacs-Trepanier, Güneş Can, Ana C Andreazza, L Trevor Young, Ayşegül Özerdem
DNA redox modulations and methylation have been associated with bipolar disorder (BD) pathophysiology. We aimed to investigate DNA redox modulation and global DNA methylation and demethylation levels in patients with BD during euthymia, mania or depression in comparison to non-psychiatric controls. The roles of sex and smoking as susceptibility factors for DNA redox modulations and global DNA methylation and demethylation were also explored. Levels of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed in DNA samples of 75 patients with DSM-IV BD type I (37 euthymic, 18 manic, 20 depressive) in comparison to 60 non-psychiatric controls...
March 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29382202/sulfinate-based-selective-labeling-of-5-hydroxymethylcytosine-application-to-biotin-pull-down-assay
#18
Qiong Wu, Suyog Madhav Amrutkar, Fangwei Shao
We developed an enzyme-free, chemical method to selectively label the epigenetic base, 5-hydroxymethylcytosine (hmC) with versatile sulfinate reagents in aqueous solvent under mild reaction conditions. This method allows efficient single step conjugation of biotin to hmC site in DNA for enrichment and pull down assays.
February 21, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29374200/interplay-between-tets-and-micrornas-in-the-adult-brain-for-memory-formation
#19
Eloïse A Kremer, Niharika Gaur, Melissa A Lee, Olivia Engmann, Johannes Bohacek, Isabelle M Mansuy
5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET) proteins. 5-hmC is widely present in the brain and is subjected to dynamic regulation during development and upon neuronal activity. It was recently shown to be involved in memory processes but currently, little is known about how it is controlled in the brain during memory formation. Here, we show that Tet3 is selectively up-regulated by activity in hippocampal neurons in vitro, and after formation of fear memory in the hippocampus...
January 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29364877/tet2-promotes-pathogen-infection-induced-myelopoiesis-through-mrna-oxidation
#20
Qicong Shen, Qian Zhang, Yang Shi, Qingzhu Shi, Yanyan Jiang, Yan Gu, Zhiqing Li, Xia Li, Kai Zhao, Chunmei Wang, Nan Li, Xuetao Cao
Varieties of RNA modification form the epitranscriptome for post-transcriptional regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA (mRNA) under physiological conditions. The function of RNA 5-hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins in Drosophila has been revealed more recently. However, the turnover and function of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid malignancies mostly in an enzymatic activity-dependent manner, and is important in resolving inflammatory response in an enzymatic activity-independent way...
February 1, 2018: Nature
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