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https://www.readbyqxmd.com/read/28332209/quantitation-and-mapping-of-the-epigenetic-marker-5-hydroxymethylcytosine
#1
Ying Qing, Zhiqi Tian, Ying Bi, Yongyao Wang, Jiangang Long, Chun-Xiao Song, Jiajie Diao
We here review primary methods used in quantifying and mapping 5-hydroxymethylcytosine (5hmC), including global quantification, restriction enzyme-based detection, and methods involving DNA-enrichment strategies and the genome-wide sequencing of 5hmC. As discovered in the mammalian genome in 2009, 5hmC, oxidized from 5-methylcytosine (5mC) by ten-eleven translocation (TET) dioxygenases, is increasingly being recognized as a biomarker in biological processes from development to pathogenesis, as its various detection methods have shown...
March 23, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28325772/tet3-mediated-dna-oxidation-promotes-atr-dependent-dna-damage-response
#2
Dewei Jiang, Shu Wei, Fei Chen, Ying Zhang, Jiali Li
An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28294608/an-engineered-split-tet2-enzyme-for-inducible-epigenetic-remodeling
#3
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/28277978/targeted-dna-demethylation-in-human-cells-by-fusion-of-a-plant-5-methylcytosine-dna-glycosylase-to-a-sequence-specific-dna-binding-domain
#4
Jara Teresa Parrilla-Doblas, Rafael R Ariza, Teresa Roldán-Arjona
DNA methylation is a crucial epigenetic mark associated to gene silencing, and its targeted removal is a major goal of epigenetic editing. In animal cells, DNA demethylation involves iterative 5mC oxidation by TET enzymes followed by replication-dependent dilution and/or replication-independent DNA repair of its oxidized derivatives. In contrast, plants use specific DNA glycosylases that directly excise 5mC and initiate its substitution for unmethylated C in a base excision repair process. In this work, we have fused the catalytic domain of Arabidopsis ROS1 5mC DNA glycosylase (ROS1_CD) to the DNA binding domain of yeast GAL4 (GBD)...
February 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28267381/dynamics-of-5-carboxylcytosine-during-hepatic-differentiation-potential-general-role-for-active-demethylation-by-dna-repair-in-lineage-specification
#5
Lara C Lewis, Peggy Cho Kiu Lo, Jeremy M Foster, Nan Dai, Ivan R Corrêa, Paulina M Durczak, Gary Duncan, Ashley Ramsawhook, Guruprasad Padur Aithal, Chris Denning, Nicholas R F Hannan, Alexey Ruzov
Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operative in this system; however, it is still unknown if TDG/BER-dependent demethylation is utilized during other types of cellular differentiation...
March 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28261325/technical-advances-in-global-dna-methylation-analysis-in-human-cancers
#6
REVIEW
Basudev Chowdhury, Il-Hoon Cho, Joseph Irudayaraj
Prototypical abnormalities of genome-wide DNA methylation constitute the most widely investigated epigenetic mechanism in human cancers. Errors in the cellular machinery to faithfully replicate the global 5-methylcytosine (5mC) patterns, commonly observed during tumorigenesis, give rise to misregulated biological pathways beneficial to the rapidly propagating tumor mass but deleterious to the healthy tissues of the affected individual. A growing body of evidence suggests that the global DNA methylation levels could serve as utilitarian biomarkers in certain cancer types...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/28248100/a-synthetically-tunable-system-to-control-mlct-excited-state-lifetimes-and-spin-states-in-iron-ii-polypyridines
#7
Steven M Fatur, Samuel G Shepard, Robert F Higgins, Matthew P Shores, Niels H Damrauer
2,2':6',2″-Terpyridyl (tpy) ligands modified by fluorine (dftpy), chlorine (dctpy), or bromine (dbtpy) substitution at the 6- and 6″-positions are used to synthesize a series of bis-homoleptic Fe(II) complexes. Two of these species, [Fe(dctpy)2](2+) and [Fe(dbtpy)2](2+), which incorporate the larger dctpy and dbtpy ligands, assume a high-spin quintet ground state due to substituent-induced intramolecular strain. The smaller fluorine atoms in [Fe(dftpy)2](2+) enable spin crossover with a T1/2 of 220 K and a mixture of low-spin (singlet) and high-spin (quintet) populations at room temperature...
March 14, 2017: Journal of the American Chemical Society
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/28236006/histone-h3-and-h4-acetylation-patterns-are-more-dynamic-than-those-of-dna-methylation-in-brachypodium-distachyon-embryos-during-seed-maturation-and-germination
#9
Elzbieta Wolny, Agnieszka Braszewska-Zalewska, Daria Kroczek, Robert Hasterok
The transition of seeds from a dry to a metabolically active state requires significant changes in both the spatial and temporal patterns of gene expression, and this transcriptional reprogramming involves various modifications of the chromatin structure. There are several factors that can greatly influence the structure of chromatin, one of which is the chemical modifications of histone proteins and DNA itself. In this study, we analysed the distribution of three epigenetic markers, i.e. acetylation of histone H4 (H4K16ac) and histone H3 (H3K18ac) as well as DNA methylation (5mC) in Brachypodium distachyon embryos during the four stages of seed development-maturation, desiccation (quiescence), imbibition and germination...
February 24, 2017: Protoplasma
https://www.readbyqxmd.com/read/28229992/increased-5-hydroxymethylcytosine-and-ten-eleven-translocation-protein-expression-in-ultraviolet-b-irradiated-hacat-cells
#10
Dan Wang, Jin-Hua Huang, Qing-Hai Zeng, Can Gu, Shu Ding, Jian-Yun Lu, Jing Chen, Sheng-Bo Yang
BACKGROUND: DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine (5mC) is catalyzed to 5- hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins. Recent studies have revealed that aberrant TETs expression or 5hmC level may play important roles in the occurrence and development of various pathological and physiological processes including cancer and aging. This study aimed to explore the relation between aberrant DNA hydroxymethylation with skin photoaging and to investigate the levels of TETs, 5mC, and 5hmC expression 24 h after 40 mJ/cm2 and 80 mJ/cm2 doses of ultraviolet B (UVB) irradiation to HaCaT cells...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28229923/epigenetic-regulation-of-reln-and-gad1-in-the-frontal-cortex-fc-of-autism-spectrum-disorder-asd-subjects
#11
Adrian Zhubi, Ying Chen, Alessandro Guidotti, Dennis R Grayson
Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain...
February 13, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#12
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28228845/histone-and-dna-methylation-control-by-h3-serine-10-threonine-11-phosphorylation-in-the-mouse-zygote
#13
Jie Lan, Konstantin Lepikhov, Pascal Giehr, Joern Walter
BACKGROUND: In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of histone H3 variants and distinct patterns of DNA and histone modifications. The molecular mechanisms linking histone variant-specific modifications and DNA methylation reprogramming during the first cell cycle remain to be clarified. RESULTS: Here, we show that the degree and distribution of H3K9me2 and of DNA modifications (5mC/5hmC) are influenced by the phosphorylation status of H3S10 and H3T11...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28219769/epitranscriptomic-regulation-of-viral-replication
#14
REVIEW
Camila Pereira-Montecinos, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
RNA plays central roles in biology and novel functions and regulation mechanisms are constantly emerging. To accomplish some of their functions within the cell, RNA molecules undergo hundreds of chemical modifications from which N6-methyladenosine (m(6)A), inosine (I), pseudouridine (ψ) and 5-methylcytosine (5mC) have been described in eukaryotic mRNA. Interestingly, the m(6)A modification was shown to be reversible, adding novel layers of regulation of gene expression through what is now recognized as epitranscriptomics...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28167661/distinct-roles-for-tet-family-proteins-in-regulating-human-erythropoiesis
#15
Hongxia Yan, Yaomei Wang, Xiaoli Qu, Jie Li, John Hale, Yumin Huang, Chao An, Julien Papoin, Xinhua Guo, Lixiang Chen, Qiaozhen Kang, Wei Li, Vincent P Schulz, Patrick G Gallagher, Christopher D Hillyer, Narla Mohandas, Xiuli An
The TET family of proteins plays important roles in a wide range of biological processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC). However, their function in erythropoiesis has remained unclear. We show here that TET2 and TET3, but not TET1 are expressed in human erythroid cells and we explore the role of these proteins in erythropoiesis. Knockdown experiments revealed that TET2 and TET3 have different functions. Suppression of TET3 expression in human CD34(+) cells markedly impaired terminal erythroid differentiation, as reflected by increased apoptosis, generation of bi/multinucleated polychromatic/orthochromatic erythroblasts and impaired enucleation, though without effect on erythroid progenitors...
February 6, 2017: Blood
https://www.readbyqxmd.com/read/28149330/what-s-in-a-name-context-dependent-significance-of-global-methylation-measures-in-human-health-and-disease
#16
Regan Vryer, Richard Saffery
The study of DNA methylation in development and disease has 'exploded' as a field in recent years, with three major classes of measurement now routine. These encompass (i) locus-specific, (ii) genome-scale/wide and (iii) 'global' methylation approaches. Measures of global methylation refer to the level of 5-methylcytosine (5mC) content in a sample relative to total cytosine. Despite this, several other measures are often referred to as 'global', with the underlying assumption that they accurately reflect 5mC content...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28141796/epigenomic-landscape-of-5-hydroxymethylcytosine-reveals-its-transcriptional-regulation-of-lncrnas-in-colorectal-cancer
#17
Hanyang Hu, Maoguo Shu, Lin He, Xueyuan Yu, Xiangyu Liu, Yalin Lu, Yinghong Chen, Xiaoping Miao, Xiaohua Chen
BACKGROUND: DNA methylation at the 5 position of cytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation family. The loss of global levels of 5hmC has been regarded as a hallmark in various cancers. 5-hydroxymethylcytosine is distributed at protein-coding gene bodies and promoters; however, the role and distribution of 5hmC at long non-coding RNAs (lncRNAs) is not clear. We investigated the distribution and regulatory roles of 5hmC for lncRNAs in colorectal cancer (CRC)...
February 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28130236/h-o-ta-estimation-of-dna-methylation-and-hydroxylation-levels-and-efficiencies-from-time-course-data
#18
Charalampos Kyriakopoulos, Pascal Giehr, Verena Wolf
MOTIVATION: Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates. RESULTS: We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing...
January 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28125731/correlated-5-hydroxymethylcytosine-5hmc-and-gene-expression-profiles-underpin-gene-and-organ-specific-epigenetic-regulation-in-adult-mouse-brain-and-liver
#19
I-Hsuan Lin, Yi-Fan Chen, Ming-Ta Hsu
BACKGROUND: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology. METHODS: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28125717/epigenetic-alterations-affecting-transcription-factors-and-signaling-pathways-in-stromal-cells-of-endometriosis
#20
Iveta Yotova, Emily Hsu, Catherine Do, Aulona Gaba, Matthias Sczabolcs, Sabine Dekan, Lukas Kenner, Rene Wenzl, Benjamin Tycko
Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains...
2017: PloS One
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