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Designer chromatin

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https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#1
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27923917/metadherin-astrocyte-elevated-gene-1-positively-regulates-the-stability-and-function-of-forkhead-box-m1-during-tumorigenesis
#2
Lixuan Yang, Kejun He, Sheng Yan, Yibing Yang, Xinya Gao, Maolei Zhang, Zhibo Xia, Zhengsong Huang, Suyun Huang, Nu Zhang
BACKGROUND: Forkhead box M1 (FOXM1) is overexpressed and activates numerous oncoproteins in tumors. However, the mechanism by which the FOXM1 protein aberrantly accumulates in human cancer remains uncertain. This study was designed to clarify the upstream signaling pathway(s) that regulate FOXM1 protein stability and transcriptional activity. METHODS: Mass spectrometry and immunoprecipitation were performed to identify the FOXM-metadherin (MTDH) interaction. In vivo and in vitro ubiquitination assays were conducted to test the effect of MTDH on FOXM1 stability...
December 6, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27923366/3c-digital-pcr-for-quantification-of-chromatin-interactions
#3
Meijun Du, Liang Wang
BACKGROUND: Chromosome conformation capture (3C) is a powerful and widely used technique for detecting the physical interactions between chromatin regions in vivo. The principle of 3C is to convert physical chromatin interactions into specific DNA ligation products, which are then detected by quantitative polymerase chain reaction (qPCR). However, 3C-qPCR assays are often complicated by the necessity of normalization controls to correct for amplification biases. In addition, qPCR is often limited to a certain cycle number, making it difficult to detect fragment ligations with low frequency...
December 6, 2016: BMC Molecular Biology
https://www.readbyqxmd.com/read/27906449/differential-mutation-frequencies-in-metastatic-cutaneous-squamous-cell-carcinomas-versus-primary-tumors
#4
Ayse Selen Yilmaz, Hatice Gulcin Ozer, Jessica L Gillespie, Dawn C Allain, Madison N Bernhardt, Karina Colossi Furlan, Leticia T F Castro, Sara B Peters, Priyadharsini Nagarajan, Stephen Y Kang, O Hans Iwenofu, Thomas Olencki, Theodoros N Teknos, Amanda Ewart Toland
BACKGROUND: Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but typically is associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die each year of this disease. METHODS: Because it is difficult to predict which cSCCs are more likely to metastasize, and because to the best of the authors' knowledge there are no targeted therapies specifically designated for patients with metastatic cSCC, exome and/or targeted sequencing of 18 metastatic and 10 primary cSCCs was performed to identify mutations that were more frequent in metastatic tumors and might be targeted for therapeutic benefit...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27899642/the-ucsc-genome-browser-database-2017-update
#5
Cath Tyner, Galt P Barber, Jonathan Casper, Hiram Clawson, Mark Diekhans, Christopher Eisenhart, Clayton M Fischer, David Gibson, Jairo Navarro Gonzalez, Luvina Guruvadoo, Maximilian Haeussler, Steve Heitner, Angie S Hinrichs, Donna Karolchik, Brian T Lee, Christopher M Lee, Parisa Nejad, Brian J Raney, Kate R Rosenbloom, Matthew L Speir, Chris Villarreal, John Vivian, Ann S Zweig, David Haussler, Robert M Kuhn, W James Kent
Since its 2001 debut, the University of California, Santa Cruz (UCSC) Genome Browser (http://genome.ucsc.edu/) team has provided continuous support to the international genomics and biomedical communities through a web-based, open source platform designed for the fast, scalable display of sequence alignments and annotations landscaped against a vast collection of quality reference genome assemblies. The browser's publicly accessible databases are the backbone of a rich, integrated bioinformatics tool suite that includes a graphical interface for data queries and downloads, alignment programs, command-line utilities and more...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27881582/the-expanding-role-of-the-bcl6-oncoprotein-as-a-cancer-therapeutic-target
#6
Mariano G Cardenas, Erin Oswald, Wenbo Yu, Fengtian Xue, Alexander D MacKerell, Ari M Melnick
BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes, and then repressing these genes by recruiting several different chromatin modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly a number of compounds have been designed to bind to BCL6 and block corepressor recruitment...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27863463/the-chip-seq-tools-and-web-server-a-resource-for-analyzing-chip-seq-and-other-types-of-genomic-data
#7
Giovanna Ambrosini, René Dreos, Sunil Kumar, Philipp Bucher
BACKGROUND: ChIP-seq and related high-throughput chromatin profilig assays generate ever increasing volumes of highly valuable biological data. To make sense out of it, biologists need versatile, efficient and user-friendly tools for access, visualization and itegrative analysis of such data. RESULTS: Here we present the ChIP-Seq command line tools and web server, implementing basic algorithms for ChIP-seq data analysis starting with a read alignment file. The tools are optimized for memory-efficiency and speed thus allowing for processing of large data volumes on inexpensive hardware...
November 18, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27855103/hyaluronic-acid-binding-sperm-selection-for-assisted-reproduction-treatment-habselect-study-protocol-for-a-multicentre-randomised-controlled-trial
#8
K D Witt, L Beresford, S Bhattacharya, K Brian, A Coomarasamy, R Hooper, J Kirkman-Brown, Y Khalaf, S E Lewis, A Pacey, S Pavitt, R West, D Miller
INTRODUCTION: The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial is to determine the efficacy of hyaluronic acid (HA)-selection of sperm versus conventionally selected sperm prior to ICSI on live birth rate (LBR)...
October 7, 2016: BMJ Open
https://www.readbyqxmd.com/read/27847140/a-novel-adamantane-thiadiazole-derivative-induces-mitochondria-mediated-apoptosis-in-lung-carcinoma-cell-line
#9
Ayat G Ali, Magda F Mohamed, Abdou O Abdelhamid, Mervat S Mohamed
The interaction of organic compounds with apoptosis regulatory proteins is an attractive field of research because of its relevance in the development of new chemotherapeutic agents for cancer treatment. Our group designed four new adamantane thiadiazole derivatives (ATDs). The four ATDs were theoretically tested for their binding affinities to a model of an apoptosis inhibitor protein using molecular modeling. ATD-4 which interacted with the highest binding affinity was synthesized and characterized. The in vitro cytotoxicity of ATD-4 against different cancer cell lines as well as normal cell line was determined and compared with 5-fluorouracil as a standard positive control...
November 5, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27835030/a-mad-bayes-algorithm-for-state-space-inference-and-clustering-with-application-to-querying-large-collections-of-chip-seq-data-sets
#10
Chandler Zuo, Kailei Chen, Sündüz Keleş
Current analytic approaches for querying large collections of chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from multiple cell types rely on individual analysis of each data set (i.e., peak calling) independently. This approach discards the fact that functional elements are frequently shared among related cell types and leads to overestimation of the extent of divergence between different ChIP-seq samples. Methods geared toward multisample investigations have limited applicability in settings that aim to integrate 100s to 1000s of ChIP-seq data sets for query loci (e...
November 11, 2016: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/27834128/studies-on-non-synonymous-polymorphisms-altering-human-dna-topoisomerase-ii-alpha-interaction-with-amsacrine-and-mitoxantrone-an-in-silico-approach
#11
Farzaneh Mohamadi Farsani, Mohamad Reza Ganjalikhany, Sadeq Vallian
DNA topoisomerase II-α (Top2-α), an essential enzyme for the management of DNA during replication, transcription, recombination, and chromatin remodeling, is one of the most important anticancer targets. Numerous molecules have been designed as Top2-α inhibitors. However, several studies have shown that polymorphisms and mutations in Top2 have conferred resistance to most of these anticancer drugs. The aim of this study was to computationally examine the mechanisms by which genomic variations in Top2-α could affect its resistance to Amsacrine and Mitoxantrone as important inhibitors of the enzyme...
November 9, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27832085/measuring-sperm-dna-fragmentation-and-clinical-outcomes-of-medically-assisted-reproduction-a-systematic-review-and-meta-analysis
#12
Maartje Cissen, Madelon van Wely, Irma Scholten, Steven Mansell, Jan Peter de Bruin, Ben Willem Mol, Didi Braat, Sjoerd Repping, Geert Hamer
Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to test sperm DNA fragmentation such as the sperm chromatin structure assay (SCSA), the sperm chromatin dispersion (SCD) test, the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay and the single cell gel electrophoresis (Comet) assay. We performed a systematic review and meta-analysis to assess the value of measuring sperm DNA fragmentation in predicting chance of ongoing pregnancy with IVF or ICSI...
2016: PloS One
https://www.readbyqxmd.com/read/27830652/synthetic-genome-readers-target-clustered-binding-sites-across-diverse-chromatin-states
#13
Graham S Erwin, Matthew P Grieshop, Devesh Bhimsaria, Truman J Do, José A Rodríguez-Martínez, Charu Mehta, Kanika Khanna, Scott A Swanson, Ron Stewart, James A Thomson, Parameswaran Ramanathan, Aseem Z Ansari
Targeting the genome with sequence-specific DNA-binding molecules is a major goal at the interface of chemistry, biology, and precision medicine. Polyamides, composed of N-methylpyrrole and N-methylimidazole monomers, are a class of synthetic molecules that can be rationally designed to "read" specific DNA sequences. However, the impact of different chromatin states on polyamide binding in live cells remains an unresolved question that impedes their deployment in vivo. Here, we use cross-linking of small molecules to isolate chromatin coupled to sequencing to map the binding of two bioactive and structurally distinct polyamides to genomes directly within live H1 human embryonic stem cells...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27821221/chromatin-fractal-organization-textural-patterns-and-circularity-of-nuclear-envelope-in-adrenal-zona-fasciculata-cells
#14
Igor Pantic, Dejan Nesic, Milos Basailovic, Mila Cetkovic, Sanja Mazic, Jelena Suzic-Lazic, Martin Popevic
Despite previous research efforts in the fields of histology and cell physiology, the relationship between chromatin structural organization and nuclear shape remains unclear. The aim of this research was to test the existence and strength of correlations between mathematical parameters of chromatin microarchitecture and roundness of the nuclear envelope. On a sample of 240 nuclei of adrenal zona fasciculata cells stained using the DNA-specific Feulgen method, we quantified fractal parameters such as fractal dimension and lacunarity, as well as textural parameters such as angular second moment (ASM), entropy, inverse difference moment, contrast, and variance...
November 8, 2016: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/27788138/towards-a-safer-more-randomized-lentiviral-vector-integration-profile-exploring-artificial-ledgf-chimeras
#15
Lenard S Vranckx, Jonas Demeulemeester, Zeger Debyser, Rik Gijsbers
The capacity to integrate transgenes into the host cell genome makes retroviral vectors an interesting tool for gene therapy. Although stable insertion resulted in successful correction of several monogenic disorders, it also accounts for insertional mutagenesis, a major setback in otherwise successful clinical gene therapy trials due to leukemia development in a subset of treated patients. Despite improvements in vector design, their use is still not risk-free. Lentiviral vector (LV) integration is directed into active transcription units by LEDGF/p75, a host-cell protein co-opted by the viral integrase...
2016: PloS One
https://www.readbyqxmd.com/read/27782467/a-fast-open-source-implementation-of-adaptive-biasing-potentials-uncovers-a-ligand-design-strategy-for-the-chromatin-regulator-brd4
#16
Bradley M Dickson, Parker W de Waal, Zachary H Ramjan, H Eric Xu, Scott B Rothbart
In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1 μs-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state...
October 21, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27768875/high-resolution-mapping-of-rna-binding-regions-in-the-nuclear-proteome-of-embryonic-stem-cells
#17
Chongsheng He, Simone Sidoli, Robert Warneford-Thomson, Deirdre C Tatomer, Jeremy E Wilusz, Benjamin A Garcia, Roberto Bonasio
Interactions between noncoding RNAs and chromatin proteins play important roles in gene regulation, but the molecular details of most of these interactions are unknown. Using protein-RNA photocrosslinking and mass spectrometry on embryonic stem cell nuclei, we identified and mapped, at peptide resolution, the RNA-binding regions in ∼800 known and previously unknown RNA-binding proteins, many of which are transcriptional regulators and chromatin modifiers. In addition to known RNA-binding motifs, we detected several protein domains previously unknown to function in RNA recognition, as well as non-annotated and/or disordered regions, suggesting that many functional protein-RNA contacts remain unexplored...
October 20, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27761826/evaluation-of-innate-immune-gene-expression-following-hdac-inhibitor-treatment-by-high-throughput-qpcr-and-phosflow-cytometry
#18
David Olagnier, Cindy Chiang, John Hiscott
The dynamics of chromatin structure contribute to the regulation of gene transcription and in part, the changes in chromatin structure associated with gene activation/repression are a function of the state of histone acetylation. Histone deacetylases (HDACs) deacetylate histone tails leading to a more compact structure of chromatin that in turn represses gene transcription. Given the rapid activation and/or repression of gene networks following microbial infection, the role of HDACs in the epigenetic regulation of genes involved in the innate and adaptive immune responses has become an area of extensive research...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27756290/evaluating-the-use-of-a-cpg-free-promoter-for-long-term-recombinant-protein-expression-stability-in-chinese-hamster-ovary-cells
#19
Steven C L Ho, Esther Y C Koh, Benjamin P C Soo, Mariati, Sheng-Hao Chao, Yuansheng Yang
BACKGROUND: Methylated CpG dinucleotides in promoters are associated with the loss of gene expression in recombinant Chinese hamster ovary (CHO) cells during large-scale commercial manufacturing. We evaluated a promoter devoid of CpG dinucleotides, CpGfree, in parallel with a similar CpG containing promoter, CpGrich, for their ability to maintain the expression of recombinant enhanced green fluorescent protein (EGFP) after 8 weeks of culturing. RESULTS: While the promoters gave similar transient expression levels, CpGfree clones had significantly higher average stable expression possibly due to increased resistance to early silencing during integration into the chromosome...
October 18, 2016: BMC Biotechnology
https://www.readbyqxmd.com/read/27730230/an-evolution-based-dna-binding-residue-predictor-using-a-dynamic-query-driven-learning-scheme
#20
H Chai, J Zhang, G Yang, Z Ma
DNA-binding proteins play a pivotal role in various biological activities. Identification of DNA-binding residues (DBRs) is of great importance for understanding the mechanism of gene regulations and chromatin remodeling. Most traditional computational methods usually construct their predictors on static non-redundant datasets. They excluded many homologous DNA-binding proteins so as to guarantee the generalization capability of their models. However, those ignored samples may potentially provide useful clues when studying protein-DNA interactions, which have not obtained enough attention...
October 12, 2016: Molecular BioSystems
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