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methyl-CpG binding domain protein

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https://www.readbyqxmd.com/read/28637186/cpg-and-methylation-dependent-dna-binding-and-dynamics-of-the-methylcytosine-binding-domain-2-protein-at-the-single-molecule-level
#1
Hai Pan, Stephanie M Bilinovich, Parminder Kaur, Robert Riehn, Hong Wang, David C Williams
The methylcytosine-binding domain 2 (MBD2) protein recruits the nucleosome remodeling and deacetylase complex (NuRD) to methylated DNA to modify chromatin and regulate transcription. Importantly, MBD2 functions within CpG islands that contain 100s to 1000s of potential binding sites. Since NuRD physically rearranges nucleosomes, the dynamic mobility of this complex is directly related to function. In these studies, we use NMR and single-molecule atomic force microscopy and fluorescence imaging to study DNA binding dynamics of MBD2...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28580176/engineering-affinity-agents-for-the-detection-of-hemi-methylated-cpg-sites-in-dna
#2
B E Tarn, K-J Sung, H D Sikes
Wild-type methyl-CpG-binding domain (MBD) proteins specifically bind symmetrically methylated DNA sequences, and assays have been developed that use these proteins for profiling DNA methylation. Here, we use directed evolution in the yeast surface display format to identify a new protein variant that binds hemi-methylated CpG dinucleotides.
October 1, 2016: Molecular Systems Design & Engineering
https://www.readbyqxmd.com/read/28542388/targeted-dna-methylation-in-pericentromeres-with-genome-editing-based-artificial-dna-methyltransferase
#3
Taiga Yamazaki, Yu Hatano, Tetsuya Handa, Sakiko Kato, Kensuke Hoida, Rui Yamamura, Takashi Fukuyama, Takayuki Uematsu, Noritada Kobayashi, Hiroshi Kimura, Kazuo Yamagata
To study the impact of epigenetic changes on biological functions, the ability to manipulate the epigenetic status of certain genomic regions artificially could be an indispensable technology. "Epigenome editing" techniques have gradually emerged that apply TALE or CRISPR/Cas9 technologies with various effector domains isolated from epigenetic code writers or erasers such as DNA methyltransferase, 5-methylcytosine oxidase, and histone modification enzymes. Here we demonstrate that a TALE recognizing a major satellite, consisting of a repeated sequence in pericentromeres, could be fused with the bacterial CpG methyltransferase, SssI...
2017: PloS One
https://www.readbyqxmd.com/read/28531272/a-novel-isoform-of-tet1-that-lacks-a-cxxc-domain-is-overexpressed-in-cancer
#4
Charly R Good, Jozef Madzo, Bela Patel, Shinji Maegawa, Nora Engel, Jaroslav Jelinek, Jean-Pierre J Issa
TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine (5hmC), resulting in regulation of DNA methylation and gene expression. Full length TET1 (TET1FL) has a CXXC domain that binds to unmethylated CpG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation, but it also limits its ability to regulate genes outside of CGIs. Here, we report a novel isoform of TET1 (TET1ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#5
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28510608/the-biomphalaria-glabrata-dna-methylation-machinery-displays-spatial-tissue-expression-is-differentially-active-in-distinct-snail-populations-and-is-modulated-by-interactions-with-schistosoma-mansoni
#6
Kathrin K Geyer, Umar H Niazi, David Duval, Céline Cosseau, Chad Tomlinson, Iain W Chalmers, Martin T Swain, David J Cutress, Utibe Bickham-Wright, Sabrina E Munshi, Christoph Grunau, Timothy P Yoshino, Karl F Hoffmann
BACKGROUND: The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail's response to infection. METHODOLOGY/PRINCIPLE FINDINGS: Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28486614/potential-role-of-dna-methylation-as-a-facilitator-of-target-search-processes-for-transcription-factors-through-interplay-with-methyl-cpg-binding-proteins
#7
Catherine A Kemme, Rolando Marquez, Ross H Luu, Junji Iwahara
Eukaryotic genomes contain numerous non-functional high-affinity sequences for transcription factors. These sequences potentially serve as natural decoys that sequester transcription factors. We have previously shown that the presence of sequences similar to the target sequence could substantially impede association of the transcription factor Egr-1 with its targets. In this study, using a stopped-flow fluorescence method, we examined the kinetic impact of DNA methylation of decoys on the search process of the Egr-1 zinc-finger protein...
May 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28450074/structural-basis-of-mecp2-distribution-on-non-cpg-methylated-and-hydroxymethylated-dna
#8
M Jeannette Sperlazza, Stephanie M Bilinovich, Leander M Sinanan, Fatima R Javier, David C Williams
The Rett-syndrome-associated methyl-CpG-binding protein 2 (MeCP2) selectively binds methylated DNA to regulate transcription during the development of mature neurons. Like other members of the methyl-CpG-binding domain (MBD) family, MeCP2 functions through the recognition of symmetrical 5-methylcytosines in CpG (mCG) dinucleotides. Advances in base-level resolution epigenetic mapping techniques have revealed, however, that MeCP2 can bind asymmetrically methylated and hydroxymethylated CpA dinucleotides and that this alternative binding selectivity modifies gene expression in the developing mammalian brain...
April 24, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28449087/methyl-cpg-binding-domain-protein-1-regulates-localization-and-activity-of-tet1-in-a-cxxc3-domain-dependent-manner
#9
Peng Zhang, Cathia Rausch, Florian D Hastert, Boyana Boneva, Alina Filatova, Sujit J Patil, Ulrike A Nuber, Yu Gao, Xinyu Zhao, M Cristina Cardoso
Cytosine modifications diversify and structure the genome thereby controlling proper development and differentiation. Here, we focus on the interplay of the 5-methylcytosine reader Mbd1 and modifier Tet1 by analyzing their dynamic subcellular localization and the formation of the Tet oxidation product 5-hydroxymethylcytosine in mammalian cells. Our results demonstrate that Mbd1 enhances Tet1-mediated 5-methylcytosine oxidation. We show that this is due to enhancing the localization of Tet1, but not of Tet2 and Tet3 at heterochromatic DNA...
April 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28382151/ct120-a-new-potential-target-for-c-myc-in-head-and-neck-cancers
#10
Elif Baltaci, Betül Seyhan, Onur Baykara, Nur Buyru
Background: CT120 is a universally expressed protein with seven transmembrane domains. It functions in cell proliferation, survival and apoptosis by activating Raf/MEK/ERK and PI3K/Akt signaling pathways. Evidence suggests that CT120 plays important roles in lung carcinogenesis and oncogenic pathway activation. c-Myc is an important transcription factor modulating cell progression, apoptosis and cellular transformation. Previous studies have shown that MYC gene is amplified in many types of cancer including head and neck squamous cell carcinoma (HNSCC)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28348241/structure-of-the-mecp2-tblr1-complex-reveals-a-molecular-basis-for-rett-syndrome-and-related-disorders
#11
Valdeko Kruusvee, Matthew J Lyst, Ceitidh Taylor, Žygimantė Tarnauskaitė, Adrian P Bird, Atlanta G Cook
Rett syndrome (RTT) is an X-linked neurological disorder caused by mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. The majority of RTT missense mutations disrupt the interaction of the MeCP2 with DNA or the nuclear receptor corepressor (NCoR)/silencing mediator of retinoic acid and thyroid receptors (SMRT) corepressor complex. Here, we show that the "NCoR/SMRT interaction domain" (NID) of MeCP2 directly contacts transducin beta-like 1 (TBL1) and TBL1 related (TBLR1), two paralogs that are core components of NCoR/SMRT...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
#12
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
#13
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)...
April 3, 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
#14
RANDOMIZED CONTROLLED TRIAL
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...
April 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
#15
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
#16
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 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
#17
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 demethylating enzymes and co-factors that are stored during oocyte growth, concurrently with the re-methylation of the oocyte itself...
May 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
#18
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...
March 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
#19
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
#20
COMPARATIVE STUDY
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...
April 2017: Immunological Investigations
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