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https://www.readbyqxmd.com/read/29165690/the-regulatory-g4-motif-of-the-kirsten-ras-kras-gene-is-sensitive-to-guanine-oxidation-implications-on-transcription
#1
Susanna Cogoi, Annalisa Ferino, Giulia Miglietta, Erik B Pedersen, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We designed oligonucleotides mimicking the KRAS G4-motif and found that 8-oxoG impacts folding and stability of the G-quadruplex. Dimethylsulphate-footprinting showed that the G-run carrying 8-oxoG is excluded from the G-tetrads and replaced by a redundant G-run in the KRAS G4-motif...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29161028/exploring-the-active-centre-of-lsd1-corest-complex-by-molecular-dynamics-simulation-utilizing-its-co-crystallized-cofactor-tetrahydrofolate-as-a-probe
#2
Waleed A A Zalloum, Hiba M Zalloum
Epigenetic targeting of cancer is a recent era to manipulate the gene without destroying the genetic material. Lysine-specific demethylase 1 (LSD1) is one of the enzymes associated with the chromatin for post-translational modifications, where it demethylates lysine amino acid in the chromatin H3 tail. Many studies showed that inhibiting LSD1 could potentially be used to treat cancer epigenetically. LSD1 is associated with its corepressor protein CoREST, and uses tetrahydrofolate as a cofactor to accept CH2 from the demethylation process...
November 21, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29158360/chromatin-modifying-gene-mutations-in-follicular-lymphoma
#3
Michael R Green
Follicular lymphoma (FL) is an indolent malignancy of germinal center B (GCB)-cells. Although the overall survival of FL patients has recently improved with the introduction of novel therapies, there is significant heterogeneity in patient outcome and a need for rationally designed therapeutic strategies that target disease biology. Next generation sequencing studies have identified chromatin modifying gene (CMG) mutations as a hallmark of FL, highlighting epigenetic modifiers as an attractive therapeutic target in this disease...
November 20, 2017: Blood
https://www.readbyqxmd.com/read/29121402/incorporating-functional-genomic-information-to-enhance-polygenic-signal-and-identify-variants-involved-in-gene-by-environment-interaction-for-young-adult-alcohol-problems
#4
Jessica E Salvatore, Jeanne E Savage, Peter Barr, Aaron R Wolen, Fazil Aliev, Eero Vuoksimaa, Antti Latvala, Lea Pulkkinen, Richard J Rose, Jaakko Kaprio, Danielle M Dick
BACKGROUND: Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment interaction (G×E) effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse, and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G×E effects. METHODS: We examined these questions in the young adult FinnTwin12 sample (n=1170)...
November 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29115470/dimethylation-of-histone-3-lysine-9-is-sensitive-to-the-epileptic-activity-and-affects-the-transcriptional-regulation-of-the-potassium-channel-kcnj10-gene-in-epileptic-rats
#5
Shao-Ping Zhang, Man Zhang, Hong Tao, Yan Luo, Tao He, Chun-Hui Wang, Xiao-Cheng Li, Ling Chen, Lin-Na Zhang, Tao Sun, Qi-Kuan Hu
Potassium channels can be affected by epileptic seizures and serve a crucial role in the pathophysiology of epilepsy. Dimethylation of histone 3 lysine 9 (H3K9me2) and its enzyme euchromatic histone‑lysine N‑methyltransferase 2 (G9a) are the major epigenetic modulators and are associated with gene silencing. Insight into whether H3K9me2 and G9a can respond to epileptic seizures and regulate expression of genes encoding potassium channels is the main purpose of the present study. A total of 16 subtypes of potassium channel genes in pilocarpine‑modelled epileptic rats were screened by reverse transcription‑quantitative polymerase chain reaction, and it was determined that the expression ATP‑sensitive inward rectifier potassium channel 10 (Kcnj10) increased in hippocampus and insular cortex, while the expression of most of the other subtypes decreased...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29082483/applications-and-caveats-on-the-utilization-of-dna-specific-probes-in-cell-based-assays
#6
Roy Edward
To perform cell-based assays using fluorescence as the readout there is a fundamental need to identify individual cellular objects. In the majority of cases this requires the addition of a DNA dye or so-called nuclear counterstain and these have become integral to assay design. End-point assays can use live or fixed cells and thus it is beneficial if such reagents are cell membrane-permeant.Further, membrane-permeant DNA dyes can open new opportunities in dynamic real time assays with caveats according to the impact of their interaction with the chromatin in live cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29081688/noncoding-variants-functional-prioritization-methods-based-on-predicted-regulatory-factor-binding-sites
#7
REVIEW
Haoyue Fu, Xiangde Zhang
BACKGROUNDS: With the advent of the post genomic era, the research for the genetic mechanism of the diseases has found to be increasingly depended on the studies of the genes, the gene-networks and gene-protein interaction networks. To explore gene expression and regulation, the researchers have carried out many studies on transcription factors and their binding sites (TFBSs). Based on the large amount of transcription factor binding sites predicting values in the deep learning models, further computation and analysis have been done to reveal the relationship between the gene mutation and the occurrence of the disease...
August 2017: Current Genomics
https://www.readbyqxmd.com/read/29072391/analysis-of-arid2-gene-mutation-in-oral-squamous-cell-carcinoma
#8
Lakshmi Prabha Das, Raghuram Hari Pitty, Kannan Asokan, Krithika C L, Anandi M S, Arvind Ramanathan
Background: The ARID2 gene, encoding a sub unit of the chromatin remodelling complex, has a possible tumour suppressor function and has been found to be frequently mutated in various tumours, including gingivo buccal oral squamous cell carcinomas. The present study was designed to analyse the presence of ARID2 gene mutations in the distinct genetic South Indian (Dravidian) population. Materials and Methods: Genomic DNA from thirty biopsy tissue samples of histopathologically confirmed cases of oral squamous cell carcinoma (OSCC) were subjected to PCR amplification with intronic primers encompassing exons 19 and 20 of ARID2...
October 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29070525/pten-is-fundamental-for-elimination-of-leukemia-stem-cells-mediated-by-gsk126-targeting-ezh2-in-chronic-myelogenous-leukemia
#9
Jingfeng Zhou, Danian Nie, Juan Li, Xin Du, Yuhong Lu, Yangqiu Li, Chang Liu, Wei Dai, Yun Wang, Yanli Jin, Jingxuan Pan
PURPOSE: Leukemia stem cells (LSCs) are important source of tyrosine kinase inhibitor (TKI) resistance and disease relapse in chronic myelogenous leukemia (CML). Targeting LSCs may be an attractive strategy to override this thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs and clarify its underlying mechanism. Experimental Design:Human primary CML CD34+ cells and retrovirally-BCR-ABL-driven CML mouse model were employed to evaluate the effects of suppression of EZH2 by GSK126 or EZH2 specific shRNA in vitro and in vivo...
October 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29069466/mga-repository-a-curated-data-resource-for-chip-seq-and-other-genome-annotated-data
#10
René Dréos, Giovanna Ambrosini, Romain Groux, Rouayda Cavin Périer, Philipp Bucher
The Mass Genome Annotation (MGA) repository is a resource designed to store published next generation sequencing data and other genome annotation data (such as gene start sites, SNPs, etc.) in a completely standardised format. Each sample has undergone local processing in order the meet the strict MGA format requirements. The original data source, the reformatting procedure and the biological characteristics of the samples are described in an accompanying documentation file manually edited by data curators...
October 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29027170/chromatin-immunoprecipitation-of-skeletal-muscle-tissue
#11
Amarjit Saini, Carl Johan Sundberg
Chromatin immunoprecipitation (ChIP) is an invaluable method for studying interactions between histone proteins and genomic DNA regions and transcriptional regulation using antibodies to enrich genomic regions associated with these epitopes. Either to monitor the presence of histones with post-translational modifications at specific genomic locations or to measure transcription factor interactions with a candidate target gene, protein-DNA complexes are most commonly crosslinked using formaldehyde, which stabilizes these transient interactions...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29027167/characterization-of-the-nucleosome-landscape-by-micrococcal-nuclease-sequencing-mnase-seq
#12
Wieteke Anna Maria Hoeijmakers, Richárd Bártfai
MNase-seq allows the genome-wide examination of the nucleosome landscape by determination of nucleosome positioning and occupancy. Typically, native or formaldehyde fixed chromatin is subjected to digestion by micrococcal nuclease (MNase), which degrades linker DNA and yields mainly mono-nucleosomes. The resulting material can be processed directly or can be subjected to an optional chromatin immunoprecipitation step (MNase-ChIP-seq). De-crosslinked and purified DNA is then subjected to next-generation sequencing...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29027161/considerations-on-experimental-design-and-data-analysis-of-chromatin-immunoprecipitation-experiments
#13
Antonio Jordán-Pla, Neus Visa
Arguably one of the most valuable techniques to study chromatin organization, ChIP is the method of choice to map the contacts established between proteins and genomic DNA. Ever since its inception, more than 30 years ago, ChIP has been constantly evolving, improving, and expanding its capabilities and reach. Despite its widespread use by many laboratories across a wide variety of disciplines, ChIP assays can be sometimes challenging to design, and are often sensitive to variations in practical implementation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29021563/non-canonical-reader-modules-of-baz1a-promote-recovery-from-dna-damage
#14
Mariano Oppikofer, Meredith Sagolla, Benjamin Haley, Hui-Min Zhang, Sarah K Kummerfeld, Jawahar Sudhamsu, E Megan Flynn, Tianyi Bai, Jennifer Zhang, Claudio Ciferri, Andrea G Cochran
Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28981106/nlrp3-inflammasome-activation-contributes-to-vsmc-phenotypic-transformation-and-proliferation-in-hypertension
#15
Hai-Jian Sun, Xing-Sheng Ren, Xiao-Qing Xiong, Yun-Zhi Chen, Ming-Xia Zhao, Jue-Jin Wang, Ye-Bo Zhou, Ying Han, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Inflammation is involved in pathogenesis of hypertension. NLRP3 inflammasome activation is a powerful mediator of inflammatory response via caspase-1 activation. The present study was designed to determine the roles and mechanisms of NLRP3 inflammasome in phenotypic modulation and proliferation of vascular smooth muscle cells (VSMCs) in hypertension. Experiments were conducted in spontaneously hypertensive rats (SHR) and primary aortic VSMCs. NLRP3 inflammasome activation was observed in the media of aorta in SHR and in the VSMCs from SHR...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28977496/kinetics-of-poly-adp-ribosyl-ation-but-not-parp1-itself-determines-the-cell-fate-in-response-to-dna-damage-in-vitro-and-in-vivo
#16
Harald Schuhwerk, Christopher Bruhn, Kanstantsin Siniuk, Wookee Min, Suheda Erener, Paulius Grigaravicius, Annika Krüger, Elena Ferrari, Tabea Zubel, David Lazaro, Shamci Monajembashi, Kirstin Kiesow, Torsten Kroll, Alexander Bürkle, Aswin Mangerich, Michael Hottiger, Zhao-Qi Wang
One of the fastest cellular responses to genotoxic stress is the formation of poly(ADP-ribose) polymers (PAR) by poly(ADP-ribose)polymerase 1 (PARP1, or ARTD1). PARP1 and its enzymatic product PAR regulate diverse biological processes, such as DNA repair, chromatin remodeling, transcription and cell death. However, the inter-dependent function of the PARP1 protein and its enzymatic activity clouds the mechanism underlying the biological response. We generated a PARP1 knock-in mouse model carrying a point mutation in the catalytic domain of PARP1 (D993A), which impairs the kinetics of the PARP1 activity and the PAR chain complexity in vitro and in vivo, designated as hypo-PARylation...
August 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28971268/phase-i-study-of-the-combination-of-quinacrine-and-erlotinib-in-patients-with-locally-advanced-or-metastatic-non-small-cell-lung-cancer
#17
Priyanka Bhateja, Afshin Dowlati, Neelesh Sharma
Introduction Preclinical data suggest quinacrine acts as an inhibitor of FACT (facilitates chromatin transcription) complex, which may play a role in TKI (tyrosine kinase inhibitor) resistance. The aim of this Phase I study was to study the safety and assess the maximum tolerated dose of quinacrine in combination with erlotinib in non small cell lung cancer (NSCLC). Methods This was a phase I study with standard 3 + 3 dose escalation design with the primary aim of determining the maximum tolerated dose. Two of 3 patients enrolled at dose level 1 experienced dose limiting toxicity (DLT)...
October 2, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28947657/human-x-chromosome-inactivation-and-reactivation-implications-for-cell-reprogramming-and-disease
#18
REVIEW
Irene Cantone, Amanda G Fisher
X-chromosome inactivation (XCI) is an exemplar of epigenetic regulation that is set up as pluripotent cells differentiate. Once established, XCI is stably propagated, but can be reversed in vivo or by pluripotent reprogramming in vitro Although reprogramming provides a useful model for inactive X (Xi) reactivation in mouse, the relative instability and heterogeneity of human embryonic stem (ES) cells and induced pluripotent stem cells hampers comparable progress in human. Here we review studies aimed at reactivating the human Xi using different reprogramming strategies...
November 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28938744/an-improved-ivm-method-for-cumulus-oocyte-complexes-from-small-follicles-in-polycystic-ovary-syndrome-patients-enhances-oocyte-competence-and-embryo-yield
#19
F Sánchez, F Lolicato, S Romero, M De Vos, H Van Ranst, G Verheyen, E Anckaert, J E J Smitz
STUDY QUESTION: Are meiotic and developmental competence of human oocytes from small (2-8 mm) antral follicles improved by applying an optimized IVM method involving a prematuration step in presence of C-Type Natriuretic Peptide (CNP) followed by a maturation step in presence of FSH and Amphiregulin (AREG)? SUMMARY ANSWER: A strategy involving prematuration culture (PMC) in the presence of CNP followed by IVM using FSH + AREG increases oocyte maturation potential leading to a higher availability of Day 3 embryos and good-quality blastocysts for single embryo transfer...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28934465/regulation-of-chromatin-folding-by-conformational-variations-of-nucleosome-linker-dna
#20
Jenna M Buckwalter, Davood Norouzi, Anna Harutyunyan, Victor B Zhurkin, Sergei A Grigoryev
Linker DNA conformational variability has been proposed to direct nucleosome array folding into more or less compact chromatin fibers but direct experimental evidence for such models are lacking. Here, we tested this hypothesis by designing nucleosome arrays with A-tracts at specific locations in the nucleosome linkers to induce inward (AT-IN) and outward (AT-OUT) bending of the linker DNA. Using electron microscopy and analytical centrifugation techniques, we observed spontaneous folding of AT-IN nucleosome arrays into highly compact structures, comparable to those induced by linker histone H1...
September 19, 2017: Nucleic Acids Research
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