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methyl-CpG binding domain protein

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https://www.readbyqxmd.com/read/28281569/treating-triple-negative-breast-cancer-cells-with-erlotinib-plus-a-select-antioxidant-overcomes-drug-resistance-by-targeting-cancer-cell-heterogeneity
#1
Bin Bao, Cristina Mitrea, Priyanga Wijesinghe, Luca Marchetti, Emily Girsch, Rebecca L Farr, Julie L Boerner, Ramzi Mohammad, Greg Dyson, Stanley R Terlecky, Aliccia Bollig-Fischer
Among breast cancer patients, those diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or the HER2 oncogene; therefore, TNBC lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against TNBC has been put forth based on estimates that 30-60% of TNBC express high levels of EGFR. However, results from clinical trials testing EGFR inhibitors, alone or in combination with cytotoxic chemotherapy, did not improve patient outcomes...
March 10, 2017: Scientific Reports
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
#2
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/28275132/impact-of-polyunsaturated-and-saturated-fat-overfeeding-on-the-dna-methylation-pattern-in-human-adipose-tissue-a-randomized-controlled-trial
#3
Alexander Perfilyev, Ingrid Dahlman, Linn Gillberg, Fredrik Rosqvist, David Iggman, Petr Volkov, Emma Nilsson, Ulf Risérus, Charlotte Ling
Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses.Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial.Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue...
March 8, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28266632/specific-cpg-hyper-methylation-leads-to-ankrd26-gene-down-regulation-in-white-adipose-tissue-of-a-mouse-model-of-diet-induced-obesity
#4
Gregory A Raciti, Rosa Spinelli, Antonella Desiderio, Michele Longo, Luca Parrillo, Cecilia Nigro, Vittoria D'Esposito, Paola Mirra, Francesca Fiory, Vincenzo Pilone, Pietro Forestieri, Pietro Formisano, Ira Pastan, Claudia Miele, Francesco Beguinot
Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the -436 and -431 bp CpG sites (CpGs) and impaired its expression...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28252217/novel-epigenetic-controlling-of-hypoxia-pathway-related-to-overexpression-and-promoter-hypomethylation-of-tet1-and-tet2-in-rpe-cells
#5
Mohammad Reza Alivand, Zahra-Soheila Soheili, Majid Pornour, Saeed Solali, Farzaneh Sabouni
CpG methylation of DNA takes part in a specific epigenetic memory that plays crucial roles in the differentiation and abnormality of the cells. The methylation pattern aberration of genomes is affected in three ways, namely DNA methyltransferase(DNMT), Ten-eleven translocation(TET), and methyl-binding Domain(MBD) proteins. Of these, TET enzymes have recently been demonstrated to be master modifier enzymes in the DNA methylation process. Additionally, recent studies emphasize that not only do epigenetic phenomena play a role in controlling hypoxia pathway, but the hypoxia condition also triggers hypomethylation of genomes that may help with the expression of hypoxia pathway genes...
March 2, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28250235/methylation-dynamics-during-folliculogenesis-and-early-embryo-development-in-sheep
#6
Laura Masala, Giovanni Pietro Burrai, Emanuela Bellu, Federica Ariu, Luisa Bogliolo, Sergio Ledda, Daniela Bebbere
Genome-wide DNA methylation reprogramming occurs during mammalian gametogenesis and early embryogenesis. Post-fertilization demethylation of paternal and maternal genomes is considered to occur by an active and passive mechanism, respectively, in most mammals but sheep; in this species no loss of methylation was observed in either pronucleus. Post-fertilization reprogramming relies on methylating and de-methylating enzymes and co-factors that are stored during oocyte growth, concurrently with the re-methylation of the oocyte itself...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28249716/conserved-effect-of-aging-on-dna-methylation-and-association-with-ezh2-polycomb-protein-in-mice-and-humans
#7
Khyobeni Mozhui, Ashutosh K Pandey
In humans, DNA methylation at specific CpG sites can be used to estimate the 'epigenetic clock', a biomarker of aging and health. The mechanisms that regulate the aging epigenome and level of conservation are not entirely clear. We performed affinity-based enrichment with methyl-CpG binding domain protein followed by high-throughput sequencing (MBD-seq) to assay DNA methylation in mouse samples. Consistent with previous reports, aging is associated with increase in methylation at CpG islands that likely overlap regulatory regions of genes that have been implicated in cancers (e...
February 27, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28229965/atmbd6-a-methyl-cpg-binding-domain-protein-maintains-gene-silencing-in-arabidopsis-by-interacting-with-rna-binding-proteins
#8
Adwaita Prasad Parida, Amrapali Sharma, Arun Kumar Sharma
DNA methylation, mediated by double-stranded RNA, is a conserved epigenetic phenomenon that protects a genome from transposons, silences unwanted genes and has a paramount function in plant or animal development. Methyl CpG binding domain proteins are members of a class of proteins that bind to methylated DNA. The Arabidopsis thaliana genome encodes 13 methyl CpG binding domain (MBD) proteins, but the molecular/biological functions of most of these proteins are still not clear. In the present study, we identified four proteins that interact with AtMBD6...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#9
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28139759/the-intervening-domain-from-mecp2-enhances-the-dna-affinity-of-the-methyl-binding-domain-and-provides-an-independent-dna-interaction-site
#10
Rafael Claveria-Gimeno, Pilar M Lanuza, Ignacio Morales-Chueca, Olga C Jorge-Torres, Sonia Vega, Olga Abian, Manel Esteller, Adrian Velazquez-Campoy
Methyl-CpG binding protein 2 (MeCP2) preferentially interacts with methylated DNA and it is involved in epigenetic regulation and chromatin remodelling. Mutations in MeCP2 are linked to Rett syndrome, the leading cause of intellectual retardation in girls and causing mental, motor and growth impairment. Unstructured regions in MeCP2 provide the plasticity for establishing interactions with multiple binding partners. We present a biophysical characterization of the methyl binding domain (MBD) from MeCP2 reporting the contribution of flanking domains to its structural stability and dsDNA interaction...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28112929/dynamics-of-methylated-cytosine-flipping-by-uhrf1
#11
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/28100736/methyl-cpg-binding-protein-mbd1-regulates-neuronal-lineage-commitment-through-maintaining-adult-neural-stem-cell-identity
#12
Emily M Jobe, Yu Gao, Brian E Eisinger, Janessa K Mladucky, Charles C Giuliani, Laurel E Kelnhofer, Xinyu Zhao
Methyl-CpG-binding domain 1 (MBD1) belongs to a family of methyl-CpG-binding proteins that are epigenetic "readers" linking DNA methylation to transcriptional regulation. MBD1 is expressed in neural stem cells residing in the dentate gyrus of the adult hippocampus (aNSCs) and MBD1 deficiency leads to reduced neuronal differentiation, impaired neurogenesis, learning deficits, and autism-like behaviors in mice; however, the precise function of MBD1 in aNSCs remains unexplored. Here, we show that MBD1 is important for maintaining the integrity and stemness of NSCs, which is critical for their ability to generate neurons...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28094816/methylation-specific-targeting-of-a-chromatin-remodeling-complex-from-sponges-to-humans
#13
Jason M Cramer, Deborah Pohlmann, Fernando Gomez, Leslie Mark, Benjamin Kornegay, Chelsea Hall, Edhriz Siraliev-Perez, Ninad M Walavalkar, M Jeannette Sperlazza, Stephanie Bilinovich, Jeremy W Prokop, April L Hill, David C Williams
DNA cytosine methylation and methyl-cytosine binding domain (MBD) containing proteins are found throughout all vertebrate species studied to date. However, both the presence of DNA methylation and pattern of methylation varies among invertebrate species. Invertebrates generally have only a single MBD protein, MBD2/3, that does not always contain appropriate residues for selectively binding methylated DNA. Therefore, we sought to determine whether sponges, one of the most ancient extant metazoan lineages, possess an MBD2/3 capable of recognizing methylated DNA and recruiting the associated nucleosome remodeling and deacetylase (NuRD) complex...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077840/novel-gatad2b-loss-of-function-mutations-cause-intellectual-disability-in-two-unrelated-cases
#14
Xiaomei Luo, Yongyi Zou, Bo Tan, Yue Zhang, Jing Guo, Lanlan Zeng, Rui Zhang, Hu Tan, Xianda Wei, Yiqiao Hu, Yu Zheng, Desheng Liang, Lingqian Wu
GATA zinc finger domain-containing 2B (GATAD2B) is a subunit of the methyl-CpG-binding protein-1 complex (MECP1), which deacetylates methylated nucleosomes and regresses transcriptional activity. Recently, GATAD2B has been elucidated as a candidate gene in patients with intellectual disability (ID). In this study, we identified two novel heterozygous frameshift mutations of GATAD2B in two unrelated ID cases through next-generation sequencing (NGS). Both of the mutations c.80_81insGATGT and c.552_555delGAAA cause truncated proteins that might be detrimental to neurodevelopment...
January 12, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28035832/graphene-nanopores-for-electronic-recognition-of-dna-methylation
#15
Aditya Sarathy, Hu Qiu, Jean-Pierre Leburton
We investigate theoretically the ability of graphene nanopore membranes to detect methylated sites along a DNA molecule by electronic sheet current along the two-dimensional (2D) materials. Special emphasis is placed on the detection sensitivity changes due to pore size, shape, position, and the presence of defects around the nanopore in a membrane with constricted geometry. Enhanced sensitivity for detecting methylated CpG sites, labeled by methyl-CpG binding domain (MBD) proteins along a DNA molecule, is obtained for electronic transport through graphene midgap states caused by the constriction...
December 30, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28002732/methyl-cpg-mbd2-interaction-requires-minimum-separation-and-exhibits-minimal-sequence-specificity
#16
Blythe Moreland, Kenji Oman, John Curfman, Pearlly Yan, Ralf Bundschuh
Determining the pattern of methylation at CpG dinucleotides in a cell remains an essential component of epigenetic profiling. The correlations among methylation, gene expression, and accompanying disease have just begun to be explored. Many experiments for sensing methylation use a relatively inexpensive, high-throughput approach with a methyl-binding domain (MBD) protein that preferentially binds to methylated CpGs. Here, we characterize the cooperativity and sequence specificity of MBD2-DNA binding in a pulldown experiment revealing three potential biases in such experiments...
December 20, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27941951/inhibition-of-the-processing-of-mir-25-by-hipk2-phosphorylated-mecp2-induces-nox4-in-early-diabetic-nephropathy
#17
Hyung Jung Oh, Mitsuo Kato, Supriya Deshpande, Erli Zhang, Das Sadhan, Linda Lanting, Mei Wang, Rama Natarajan
Phosphorylated methyl-CpG binding protein2 (p-MeCP2) suppresses the processing of several microRNAs (miRNAs). Homeo-domain interacting protein kinase2 (HIPK2) phosphorylates MeCP2, a known transcriptional repressor. However, it is not known if MeCP2 and HIPK2 are involved in processing of miRNAs implicated in diabetic nephropathy. p-MeCP2 and HIPK2 levels were significantly increased, but Seven in Absentia Homolog1 (SIAH1), which mediates proteasomal degradation of HIPK2, was decreased in the glomeruli of streptozotocin injected diabetic mice...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924040/kdm2a-integrates-dna-and-histone-modification-signals-through-a-cxxc-phd-module-and-direct-interaction-with-hp1
#18
Julie Borgel, Marek Tyl, Karin Schiller, Zsofia Pusztai, Christopher M Dooley, Wen Deng, Carol Wooding, Richard J White, Tobias Warnecke, Heinrich Leonhardt, Elisabeth M Busch-Nentwich, Till Bartke
Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27894081/mbd3-inhibits-formation-of-liver-cancer-stem-cells
#19
Ruizhi Li, Qihua He, Shuo Han, Mingzhi Zhang, Jinwen Liu, Ming Su, Shiruo Wei, Xuan Wang, Li Shen
Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is essential for reprogramming somatic cells. In this study, we investigated the function of NuRD in the induction of liver CSCs. We showed that suppression of methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor complex, together with OSKM transduction, induces conversion of liver cancer cells into stem-like cells...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27849519/dna-methylation-directs-genomic-localization-of-mbd2-and-mbd3-in-embryonic-stem-cells
#20
Sarah J Hainer, Kurtis N McCannell, Jun Yu, Ly-Sha Ee, Lihua J Zhu, Oliver J Rando, Thomas G Fazzio
Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3...
November 16, 2016: ELife
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