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methyl-CpG binding domain protein

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https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#1
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
#2
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
#3
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 2, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27848899/computational-modeling-approach-in-probing-effects-of-cytosine-methylation-on-the-transcription-factor-binding-to-dna
#13
John Tenayuca, Kimberley Cousins, Shumei Yang, Lubo Zhang
Cytosine methylation at CpG dinucleotides is a chief mechanism in epigenetic modification of gene expression patterns. Previous studies demonstrated that increased CpG methylation of Sp1 sites at -268 and -346 of protein kinase C  promoter repressed the gene expression. The present study investigated the impact of CpG methylation on the Sp1 binding via molecular modeling and electrophoretic mobility shift assay. Each of the Sp1 sites contain two CpGs. Methylation of either CpG lowered the binding affinity of Sp1, whereas methylation of both CpGs produced a greater decrease in the binding affinity...
November 16, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27835581/regulatory-landscape-and-clinical-implication-of-mbd3-in-human-malignant-glioma
#14
Yi Cui, Jian Li, Ling Weng, Sara E Wirbisky, Jennifer L Freeman, Jingping Liu, Qing Liu, Xianrui Yuan, Joseph Irudayaraj
In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826844/proteins-that-read-dna-methylation
#15
Takashi Shimbo, Paul A Wade
Covalent modification of DNA via deposition of a methyl group at the 5' position on cytosine residues alters the chemical groups available for interaction in the major groove of DNA. The information content inherent in this modification alters the affinity and the specificity of DNA binding; some proteins favor interaction with methylated DNA, and others disfavor it. Molecular recognition of cytosine methylation by proteins often initiates sequential regulatory events which impact gene expression and chromatin structure...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27785392/epigenetic-alterations-in-patients-with-type-2-diabetes-mellitus
#16
S Karachanak-Yankova, R Dimova, D Nikolova, D Nesheva, M Koprinarova, S Maslyankov, R Tafradjiska, P Gateva, M Velizarova, Z Hammoudeh, N Stoynev, D Toncheva, T Tankova, I Dimova
Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years...
December 1, 2015: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/27777635/global-dna-methylation-profiling-reveals-new-insights-into-epigenetically-deregulated-protein-coding-and-long-noncoding-rnas-in-cll
#17
Santhilal Subhash, Per-Ola Andersson, Subazini Thankaswamy Kosalai, Chandrasekhar Kanduri, Meena Kanduri
BACKGROUND: Methyl-CpG-binding domain protein enriched genome-wide sequencing (MBD-Seq) is a robust and powerful method for analyzing methylated CpG-rich regions with complete genome-wide coverage. In chronic lymphocytic leukemia (CLL), the role of CpG methylated regions associated with transcribed long noncoding RNAs (lncRNA) and repetitive genomic elements are poorly understood. Based on MBD-Seq, we characterized the global methylation profile of high CpG-rich regions in different CLL prognostic subgroups based on IGHV mutational status...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27777312/mbd4-facilitates-immunoglobulin-class-switch-recombination
#18
Fernando Grigera, Robert Wuerffel, Amy L Kenter
Immunoglobulin heavy chain class switch recombination (CSR) requires targeted formation of DNA double-strand breaks (DSBs) in repetitive switch region elements followed by ligation between distal breaks. The introduction of DSBs is initiated by activation-induced cytidine deaminase (AID) and requires base excision repair (BER) and mismatch repair (MMR). The BER enzyme methyl-CpG binding domain protein 4 (MBD4) has been linked to the MMR pathway through its interaction with MutL homologue 1 (MLH1). We find that when Mbd4 exons 6 to 8 are deleted in a switching B cell line, DSB formation is severely reduced and CSR frequency is impaired...
January 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27694845/methyl-cpg-binding-domain-protein-acts-to-regulate-the-repair-of-cyclobutane-pyrimidine-dimers-on-rice-dna
#19
Changxun Fang, Weisi Chen, Chengxun Li, Xin Jian, Yingzhe Li, Hongmei Lin, Wenxiong Lin
UVB radiation causes cyclobutane pyrimidine dimers (CPDs) to form on the DNA of living organisms. This study found that overexpression of the silicon absorbance gene Lsi1 reduced the accumulation of CPDs in rice, which profited from the reactivation by photolyase. The transcript abundance of deoxyribodipyrimidine photolyase (Os10g0167600) was generally correlated with the silicon content of the rice, and the up-regulation of Os10g0167600 was found to be highest in the UVB-treated Lsi1-overexpressed (Lsi1-OX) rice...
October 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27666367/development-of-an-electrochemical-detection-system-for-measuring-dna-methylation-levels-using-methyl-cpg-binding-protein-and-glucose-dehydrogenase-fused-zinc-finger-protein
#20
Jinhee Lee, Wataru Yoshida, Koichi Abe, Kazuhiko Nakabayashi, Hironobu Wakeda, Kenichiro Hata, Christophe A Marquette, Loïc J Blum, Koji Sode, Kazunori Ikebukuro
DNA methylation level at a certain gene region is considered as a new type of biomarker for diagnosis and its miniaturized and rapid detection system is required for diagnosis. Here we have developed a simple electrochemical detection system for DNA methylation using methyl CpG-binding domain (MBD) and a glucose dehydrogenase (GDH)-fused zinc finger protein. This analytical system consists of three steps: (1) methylated DNA collection by MBD, (2) PCR amplification of a target genomic region among collected methylated DNA, and (3) electrochemical detection of the PCR products using a GDH-fused zinc finger protein...
September 17, 2016: Biosensors & Bioelectronics
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