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methyl-CpG binding domain protein

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https://www.readbyqxmd.com/read/29765857/dna-methylation-and-adult-neurogenesis
#1
REVIEW
Emily M Jobe, Xinyu Zhao
The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29761578/identification-of-the-coiled-coil-domain-as-an-essential-mbd3-element-for-preserving-lineage-commitment-potential-of-embryonic-stem-cells
#2
Masataka Hirasaki, Atsushi Ueda, Masamitsu N Asaka, Kousuke Uranishi, Ayumu Suzuki, Masakazu Kohda, Yosuke Mizuno, Yasushi Okazaki, Masazumi Nishimoto, Jafar Sharif, Haruhiko Koseki, Akihiko Okuda
Embryonic stem cells (ESCs) exhibit two salient features beneficial for regenerative medicine: unlimited self-renewal and pluripotency. Methyl-CpG-binding domain protein 3 (Mbd3), a scaffolding component of the nucleosome remodeling deacetylase complex, is a specific regulator of pluripotency, as ESCs lacking Mbd3 are defective for lineage commitment potential but retain normal self-renewal properties. However, functional similarities and dissimilarities among the three Mbd3 isoforms (a, b, and c) have not been intensively explored...
May 15, 2018: Stem Cells
https://www.readbyqxmd.com/read/29760376/the-novel-19q13-krab-zinc-finger-tumour-suppressor-znf382-is-frequently-methylated-in-oesophageal-squamous-cell-carcinoma-and-antagonises-wnt-%C3%AE-catenin-signalling
#3
Chong Zhang, Tingxiu Xiang, Shuman Li, Lin Ye, Yixiao Feng, Lijiao Pei, Lili Li, Xiangyu Wang, Ran Sun, Qian Tao, Guosheng Ren
Zinc finger proteins (ZFPs) are the largest transcription factor family in mammals. About one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs and involved in the regulation of cell differentiation/proliferation/apoptosis and neoplastic transformation. We recently identified ZNF382 as a novel KRAB-ZFP epigenetically inactivated in multiple cancers due to frequent promoter CpG methylation. However, its epigenetic alterations, biological functions/mechanism and clinical significance in oesophageal squamous cell carcinoma (ESCC) are still unknown...
May 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29741809/exogenous-il6-induces-mrna-splice-variant-mbd2_v2-to-promote-stemness-in-tp53-wild-type-african-american-pca-cells
#4
Emily A Teslow, Bin Bao, Greg Dyson, Christophe Legendre, Cristina Mitrea, Wael Sakr, John D Carpten, Isaac Powell, Aliccia Bollig-Fischer
African American men (AAM) are at higher risk of being diagnosed with prostate cancer (PCa) and are at higher risk of dying from the disease compared to European American men (EAM).We sought to better understand PCa molecular diversity that may be underlying these disparities. We performed RNA-sequencing analysis on high-grade PCa to identify genes showing differential tumor versus noncancer adjacent tissue expression patterns unique to AAM or EAM. We observed that interleukin-6 (IL6) was upregulated in the nonmalignant adjacent tissue in AAM, but in EAM IL6 expression was higher in PCa tissue...
May 9, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29693329/an-examination-of-critical-parameters-in-hybridization-based-epigenotyping-using-magnetic-microparticles
#5
Brooke E Tam, Yining Hao, Hadley D Sikes
Gene-specific promoter methylation is involved in gene silencing and is an important cancer biomarker. Cancer-specific methylation patterns have been observed and clinically validated for numerous gene promoters, but the knowledge gleaned from this large body of work is currently under-utilized in the clinic. Methylation-specific PCR is currently the gold standard method for clinical methylation assessment, but several research groups have proposed hybridization-based techniques which could be simpler to implement and provide more accurate results...
April 25, 2018: Biotechnology Progress
https://www.readbyqxmd.com/read/29567833/structural-basis-for-the-ability-of-mbd-domains-to-bind-methyl-cg-and-tg-sites-in-dna
#6
Ke Liu, Chao Xu, Ming Lei, Ally Yang, Peter Loppnau, Timothy R Hughes, Jinrong Min
Cytosine methylation is a well characterized epigenetic mark and occurs at both CG and non-CG sites in DNA. Both methylated CG (mCG)- and mCH (H = A, C, or T)-containing DNAs, especially mCAC-containing DNAs, are recognized by methyl-CpG-binding protein 2 (MeCP2) to regulate gene expression in neuron development. However, the molecular mechanism involved in the binding of methyl-CpG-binding domain (MBD) of MeCP2 to these different DNA motifs is unclear. Here, we systematically characterized the DNA-binding selectivity of the MBDs in MeCP2 and MBD1-4 with isothermal titration calorimetry-based binding assays, mutagenesis studies, and X-ray crystallography...
March 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29565710/deletion-of-mbd2-inhibits-proliferation-of-chronic-myeloid-leukaemia-blast-phase-cells
#7
Ling Cheng, Ying Tang, Xing Chen, Lei Zhao, Songya Liu, Yanna Ma, Na Wang, Kuangguo Zhou, Jianfeng Zhou, Mi Zhou
Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a "reader" of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygous deletion mutation of MBD2 using gene-editing technology in K562 cells and BV173 cells. Here, we demonstrated that the deletion of MBD2 inhibited cell proliferation capacity in vitro...
March 22, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29545913/-mbd4-frameshift-mutation-caused-by-dna-mismatch-repair-deficiency-enhances-cytotoxicity-by-trifluridine-an-active-antitumor-agent-of-tas-102-in-colorectal-cancer-cells
#8
Satoshi Suzuki, Moriya Iwaizumi, Hidetaka Yamada, Tomohiro Sugiyama, Yasushi Hamaya, Takahisa Furuta, Shigeru Kanaoka, Haruhiko Sugimura, Hiroaki Miyajima, Satoshi Osawa, John M Carethers, Ken Sugimoto
Backgrounds: Trifluridine is an active antitumor component of TAS-102 that resembles 5-fluorouracil. Although patients with advanced colorectal cancer (CRC) exhibiting a mismatch repair (MMR) deficiency reportedly do not benefit from 5-fluorouracil-based chemotherapy and we previously reported that truncated methyl-CpG binding domain protein 4 (MBD4) enhances 5-fluorouracil cytotoxicity in MMR-deficient CRC cells, little is known regarding the effect of MMR deficiency on trifluridine cytotoxicity in CRC...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29535511/reduced-mbd2-expression-enhances-airway-inflammation-in-bronchial-epithelium-in-copd
#9
Zhilin Zeng, Miao Li, Jinkun Chen, Qinghai Li, Qin Ning, Jianping Zhao, Yongjian Xu, Jungang Xie, Jun Yu
Background: Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease characterized by inflammatory cells activation and production of inflammatory mediators. Methyl-CpG-binding domain protein 2 (MBD2) plays an important role in diverse immunological disorders by regulating immune cell functions, such as differentiation and mediator secretion. However, the role of MBD2 in COPD remains unknown. Methods: MBD2 protein expression in lung tissues of patients with COPD and cigarette smoke (CS)-exposed mice were evaluated by Western blot and immunohistochemistry...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29534967/mitochondrial-dysfunction-in-dopaminergic-neurons-differentiated-from-exfoliated-deciduous-tooth-derived-pulp-stem-cells-of-a-child-with-rett-syndrome
#10
Saki Hirofuji, Yuta Hirofuji, Hiroki Kato, Keiji Masuda, Haruyoshi Yamaza, Hiroshi Sato, Fumiko Takayama, Michiko Torio, Yasunari Sakai, Shouichi Ohga, Tomoaki Taguchi, Kazuaki Nonaka
Rett syndrome is an X-linked neurodevelopmental disorder associated with psychomotor impairments, autonomic dysfunctions and autism. Patients with Rett syndrome have loss-of-function mutations in MECP2, the gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormal biogenic amine signaling and mitochondrial function have been found in patients with Rett syndrome; however, few studies have analyzed the association between these factors. This study investigated the functional relationships between mitochondria and the neuronal differentiation of the MeCP2-deficient stem cells from the exfoliated deciduous teeth of a child with Rett syndrome...
March 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29524425/effects-of-doxorubicin-on-sperm-dna-methylation-in-mouse-models-of-testicular-toxicity
#11
Kazuya Sakai, Maky Ideta-Otsuka, Hirokatsu Saito, Yuki Hiradate, Kenshiro Hara, Katsuhide Igarashi, Kentaro Tanemura
Testicular toxicity is a frequent adverse effect of cancer chemotherapy that has no effective clinical biomarker. To find new biomarkers, we focused on epigenetic mechanisms in the male germline. We investigated the DNA methylation status of the male germline during testicular toxicity induced by doxorubicin (DXR), a widely used anticancer agent. We established mouse models of early stage testicular toxicity and testicular pre-toxicity by the administration of 0.2 mg/kg and 0.02 mg/kg DXR, respectively, twice weekly for 5 weeks...
April 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29518473/gene-expression-network-regulated-by-dna-methylation-and-microrna-during-microcystin-leucine-arginine-induced-malignant-transformation-in-human-hepatocyte-l02-cells
#12
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
June 1, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29475157/the-role-of-the-n-terminal-domain-of-human-apurinic-apyrimidinic-endonuclease-1-ape1-in-dna-glycosylase-stimulation
#13
Olga A Kladova, Milena Bazlekowa-Karaban, Sonia Baconnais, Olivier Piétrement, Alexander A Ishchenko, Bakhyt T Matkarimov, Danila A Iakovlev, Andrey Vasenko, Olga S Fedorova, Eric Le Cam, Barbara Tudek, Nikita A Kuznetsov, Murat Saparbaev
The base excision repair (BER) pathway consists of sequential action of DNA glycosylase and apurinic/apyrimidinic (AP) endonuclease necessary to remove a damaged base and generate a single-strand break in duplex DNA. Human multifunctional AP endonuclease 1 (APE1, a.k.a. APEX1, HAP-1, or Ref-1) plays essential roles in BER by acting downstream of DNA glycosylases to incise a DNA duplex at AP sites and remove 3'-blocking sugar moieties at DNA strand breaks. Human 8-oxoguanine-DNA glycosylase (OGG1), methyl-CpG-binding domain 4 (MBD4, a...
April 2018: DNA Repair
https://www.readbyqxmd.com/read/29473320/epigenetic-silencing-of-rnf144a-expression-in-breast-cancer-cells-through-promoter-hypermethylation-and-mbd4
#14
Ye Zhang, Yin-Long Yang, Fang-Lin Zhang, Xiao-Hong Liao, Zhi-Min Shao, Da-Qiang Li
Emerging evidence shows that ring finger protein 144A (RNF144A), a poorly characterized member of the Ring-between-Ring (RBR) family of E3 ubiquitin ligases, is a potential tumor suppressor gene. However, its regulatory mechanism in breast cancer remains undefined. Here, we report that RNF144A promoter contains a putative CpG island and the methylation levels of RNF144A promoter are higher in primary breast tumors than those in normal breast tissues. Consistently, RNF144A promoter methylation levels are associated with its transcriptional silencing in breast cancer cells, and treatment with DNA methylation inhibitor 5-Aza-2-deoxycytidine (AZA) reactivates RNF144A expression in cells with RNF144A promoter hypermethylation...
April 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29431277/mecp2-at-hook1-mutations-in-patients-with-intellectual-disability-and-or-schizophrenia-disrupt-dna-binding-and-chromatin-compaction-in-vitro
#15
Taimoor I Sheikh, Ricardo Harripaul, Muhammad Ayub, John B Vincent
Mutations in the methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome. However, it has long been appreciated that there exists a spectrum of neuropsychiatric phenotypes associated with MECP2 variants. The most frequent Rett missense mutations are located in either the methyl-CpG-binding domain (MBD) or transcription repression domain (TRD). Clinical roles for mutations in other domains such as the intervening domain (ID) or AT-Hook domains have yet to be determined. Here, we report functional analysis of MECP2 missense mutations, located in AT-Hook1 within the ID, in a large Pakistani family with childhood onset cognitive decline and schizophrenia (SCZ), de novo in a girl with atypical Rett syndrome, and de novo in a woman with SCZ...
May 2018: Human Mutation
https://www.readbyqxmd.com/read/29428602/tyr120asp-mutation-alters-domain-flexibility-and-dynamics-of-mecp2-dna-binding-domain-leading-to-impaired-dna-interaction-atomistic-characterization-of-a-rett-syndrome-causing-mutation
#16
Ilda D'Annessa, Anna Gandaglia, Elena Brivio, Gilda Stefanelli, Angelisa Frasca, Nicoletta Landsberger, Daniele Di Marino
Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29423788/evaluation-of-extraction-methods-for-methylated-cell-free-fetal-dna-from-maternal-plasma
#17
Ji Hyae Lim, Bom Yi Lee, Jin Woo Kim, You Jung Han, Jin Hoon Chung, Min Hyoung Kim, Dong Wook Kwak, So Yeon Park, Hee Back Choi, Hyun Mee Ryu
PURPOSE: Recently, fetal placenta-specific epigenetic regions (FSERs) have been identified for quantification of cell-free fetal DNA (cff-DNA) for non-invasive prenatal testing (NIPT). The aim of this study was to evaluate the efficiencies of a column-based kit and magnetic bead-based kit for quantification of methylated FSERs from maternal plasma. METHODS: Maternal plasma was extracted from normal pregnant women within the gestational age of 10~13 weeks (n = 24)...
February 8, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29421650/first-report-of-an-unusual-novel-double-mutation-affecting-the-transcription-repression-domain-of-mecp2-and-causing-a-severe-phenotype-of-rett-syndrome-molecular-analyses-and-computational-investigation
#18
Rania Ghorbel, Raouia Ghorbel, Aida Rouissi, Nourhene Fendri-Kriaa, Ghada Ben Salah, Neila Belguith, Leila Ammar-Keskes, Neziha Gouider-Khouja, Faiza Fakhfakh
Rett syndrome is an X-linked neurodevelopmental disorder that develops a profound intellectual and motor disability and affects 1 from 10 000 to 15 000 live female births. This disease is characterized by a period of apparently normal development until 6-18 months of age when motor and communication abilities regress which is caused by mutations occurred in the X-linked MECP2 gene, encoding the methyl-CpG binding protein 2. This research study reports a molecular analysis via an exhaustive gene sequencing which reveals an unusual novel double mutation (c...
February 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29415182/arabidopsis-zinc-finger-like-protein-asymmetric-leaves2-as2-and-two-nucleolar-proteins-maintain-gene-body-dna-methylation-in-the-leaf-polarity-gene-ettin-arf3
#19
Simon Vial-Pradel, Sumie Keta, Mika Nomoto, Hiro Takahashi, Masataka Suzuki, Yuri Yokoyama, Michiko Sasabe, Shoko Kojima, Yasuomi Tada, Yasunori Machida, Chiyoko Machida
Arabidopsis ASYMMETRIC LEAVES2 (AS2) plays a critical role in leaf adaxial-abaxial partitioning by repressing expression of the abaxial-determining gene ETTIN/AUXIN RESPONSE FACTOR3 (ETT/ARF3). We previously reported that six CpG dinucleotides in its exon 6 are thoroughly methylated by METHYLTRASFERASE1, that CpG methylation levels are inversely correlated with ETT/ARF3 transcript levels, and that methylation levels at three out of six are decreased in as2-1, All these imply that AS2 is involved in epigenetic repression of ETT/ARF3 by gene body methylation...
February 5, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29402971/identification-and-caste-dependent-expression-patterns-of-dna-methylation-associated-genes-in-bombus-terrestris
#20
Beibei Li, Li Hou, Dan Zhu, Xilian Xu, Shiheng An, Xianhui Wang
DNA methylation has been proposed to play critical roles in caste fate and behavioral plasticity in bumblebees, however, there is little information on its regulatory mechanisms. Here, we identified six important genes mediating the modification of DNA methylation and determined their expression patterns in the bumblebee Bombus terrestris. There is a complete functional DNA methylation system, including four DNA methyltransferases (DNMT1a, DNMT1b, DNMT2, and DNMT3), a DNA demethylase (Ten-eleven translocation), and a methyl-CpG-binding domain protein in B...
February 5, 2018: Scientific Reports
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