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Designer chromatin

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https://www.readbyqxmd.com/read/29325176/dynamic-motif-occupancy-dynamo-analysis-identifies-transcription-factors-and-their-binding-sites-driving-dynamic-biological-processes
#1
Zheng Kuang, Zhicheng Ji, Jef D Boeke, Hongkai Ji
Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data...
January 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29304555/the-epigenetic-contribution-to-the-development-and-progression-of-vascular-diabetic-complications
#2
Hanah Rodriguez, Assam El-Osta
SIGNIFICANCE: The number of people suffering from diabetes worldwide is steadily rising. Complications from diabetes, including cardiovascular and renal disease, contribute to the high morbidity and mortality associated with this disease. Recent Advances: hyperglycaemia promotes tissue damage through diverse mechanisms involving increased production of reactive oxygen species (ROS). Increased oxidative stress drives changes in chromatin structure that mediate gene expression changes leading to the up-regulation of pro-inflammatory and pro-fibrotic mediators...
January 5, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29300860/examination-of-vdr-rxr-drip205-interaction-intranuclear-localization-and-dna-binding-in-ras-transformed-keratinocytes-and-its-implication-for-designing-optimal-vitamin-d-therapy-in-cancer
#3
Sylvester Jusu, John F Presley, Chris Williams, Sanjoy Kumar Das, Bertrand Jean-Claude, Richard Kremer
RXR occupies a central position within the nuclear receptor superfamily serving as an obligatory partner to numerous other nuclear receptors including VDR. In the present study, we examined whether phosphorylation of RXRalpha at serine 260 affects VDR/RXR and DRIP205 coactivator recruitment, interactions and binding of the VDR/ hRXRα /DRIP205 complex to chromatin. Serine 260 is a critical amino acid on the human retinoid X receptor alpha (hRXRα) that is located in close spatial proximity to regions of coactivator and corepressor interactions...
December 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29297245/super-resolution-binding-activated-localization-microscopy-through-reversible-change-of-dna-conformation
#4
Aleksander Szczurek, Udo Birk, Hans Knecht, Jurek Dobrucki, Sabine Mai, Christoph Cremer
Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine...
January 3, 2018: Nucleus
https://www.readbyqxmd.com/read/29289754/estrogen-regulated-transcription-mammary-gland-and-uterus
#5
Yasmin M Vasquez
Estrogen (E2) plays a central role in the developmental, metabolic and reproductive functions of both males and females. E2 acts via the estrogen receptor alpha (ERα) to regulate transcription of genes involved in numerous cellular functions. The E2-dependent engagement of ERα across the genome, collectively called the ERα 'cistrome', exhibits a high degree of complexity and plasticity. The ERα cistrome is defined by pioneer factors, transcription co-factors, posttranslational modifications of ERα, the chromatin environment, and cross talk with other signaling pathways...
December 29, 2017: Steroids
https://www.readbyqxmd.com/read/29286617/genistein-and-trichostatin-a-induction-of-estrogen-receptor-alpha-gene-expression-apoptosis-and-cell-growth-inhibition-in-hepatocellular-carcinoma-hepg-2-cells
#6
Masumeh Sanaei, Fraidoon Kavoosi, Habibeh Salehi
Epigenetic changes such as DNA methylation and histone acetylation play important roles in determining gene expression. Hypermethylation of CpG islands of the promoter region of tumor suppressor genes can greatly influence carcinogenesis through transcriptional silencing. Acetylation of lysine in histone tails causes relaxation of chromatin, which facilitates gene transcription, while deacetylation is associated with condensed chromatin resulting in gene silencing. DNA demethylating agents such as genistein (GE) and histone deacetylase inhibitors (HDACIs) such as trichostatin A (TSA) may strongly reactivate silenced genes and exposure to these two agents in combination is reported to enhance estrogen receptor alpha (ERα) reactivation and induction of apoptosis...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29286245/corymbulosins-i-w-cytotoxic-clerodane-diterpenes-from-the-bark-of-laetia-corymbulosa
#7
Simayijiang Aimaiti, Airi Suzuki, Yohei Saito, Shuichi Fukuyoshi, Masuo Goto, Katsunori Miyake, David J Newman, Barry R O'Keefe, Kuo-Hsiung Lee, Kyoko Nakagawa-Goto
The isolation studies of a crude MeOH/CH2Cl2 (1:1) extract (N005829) of the bark of Laetia corymbulosa yielded 15 new clerodane diterpenes, designated corymbulosins I-W (1-15), as well as four known diterpenes, 16-19. The structures of 1-15 were characterized on the basis of extensive 1D and 2D NMR and HRMS analyses. The absolute configurations of newly isolated compounds 1-15, as well as known 16-19, which were reported previously with only relative configurations, were determined through ECD experiments, X-ray analysis, chemical methods, including Mosher esterification, and comparison of their spectroscopic data...
December 29, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29281953/argo_cuda-exhaustive-gpu-based-approach-for-motif-discovery-in-large-dna-datasets
#8
Oleg V Vishnevsky, Andrey V Bocharnikov, Nikolay A Kolchanov
The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches...
December 10, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29277263/genetics-of-human-epilepsies-continuing-progress
#9
Pierre Szepetowski
Numerous epilepsy genes have been identified in the last years, mostly in the (rare) monogenic forms and thanks to the increased availability and the decreased cost of next-generation sequencing approaches. Besides the somehow expected group of epilepsy genes encoding various ion channel subunits (e.g. sodium or potassium channel subunits, or GABA receptors, or glutamate-gated NMDA receptors), more diversity has emerged recently, with novel epilepsy genes encoding proteins playing a wide range of physiological roles at the cellular and molecular levels, such as synaptic proteins, members of the mTOR pathway, or proteins involved in chromatin remodeling...
December 22, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29276797/genetic-and-epigenetic-determinants-of-inter-individual-variability-in-responses-to-toxicants
#10
Lauren Lewis, Gregory E Crawford, Terrence S Furey, Ivan Rusyn
It is well established that genetic variability has a major impact on susceptibility to common diseases, responses to drugs and toxicants, and influences disease-related outcomes. The appreciation that epigenetic marks also vary across the population is growing with more data becoming available from studies in humans and model organisms. In addition, the links between genetic variability, toxicity outcomes and epigenetics are being actively explored. Recent studies demonstrate that gene-by-environment interactions involve both chromatin states and transcriptional regulation, and that epigenetics provides important mechanistic clues to connect expression-related quantitative trait loci (QTL) and disease outcomes...
October 2017: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/29273061/diagnosis-and-treatment-of-alt-tumors-is-trabectedin-a-new-therapeutic-option
#11
REVIEW
Luca Pompili, Carlo Leonetti, Annamaria Biroccio, Erica Salvati
Telomeres are specialized nucleoprotein structures responsible for protecting chromosome ends in order to prevent the loss of genomic information. Telomere maintenance is required for achieving immortality by neoplastic cells. While most cancer cells rely on telomerase re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively referred to as Alternative Lengthening of Telomeres (ALT). ALT mechanisms involve different types of homology-directed telomere recombination and synthesis...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29251421/recognition-of-oxidized-5-methylcytosine-derivatives-in-dna-by-natural-and-engineered-protein-scaffolds
#12
REVIEW
Álvaro Muñoz-López, Daniel Summerer
Methylation of genomic cytosine to 5-methylcytosine is a central regulatory element of mammalian gene expression with important roles in development and disease. 5-methylcytosine can be actively reversed to cytosine via oxidation to 5-hydroxymethyl-, 5-formyl-, and 5-carboxylcytosine by ten-eleven-translocation dioxygenases and subsequent base excision repair or replication-dependent dilution. Moreover, the oxidized 5-methylcytosine derivatives are potential epigenetic marks with unique biological roles. Key to a better understanding of these roles are insights into the interactions of the nucleobases with DNA-binding protein scaffolds: Natural scaffolds involved in transcription, 5-methylcytosine-reading and -editing as well as general chromatin organization can be selectively recruited or repulsed by oxidized 5-methylcytosines, forming the basis of their biological functions...
December 18, 2017: Chemical Record: An Official Publication of the Chemical Society of Japan ... [et Al.]
https://www.readbyqxmd.com/read/29233856/structure-of-the-arabidopsis-jmj14-h3k4me3-complex-provides-insight-into-the-substrate-specificity-of-kdm5-subfamily-histone-demethylases
#13
Zhenlin Yang, Qi Qiu, Wei Chen, Bei Jia, Xiaomei Chen, Hongmiao Hu, Kaixuan He, Xian Deng, Sisi Li, W Andy Tao, XiaoFeng Cao, Jiamu Du
In chromatin, histone methylation affects the epigenetic regulation of multiple processes in animals and plants and is modulated by the activities of histone methyltransferases and histone demethylases. The jumonji domain-containing histone demethylases have diverse functions and can be classified into several subfamilies. In humans, the jumonji domain-containing Lysine (K)-Specific Demethylase 5/Jumonji and ARID Domain Protein (KDM5/JARID) subfamily demethylases are specific for histone 3 lysine 4 trimethylation (H3K4me3) and are important drug targets for cancer treatment...
December 12, 2017: Plant Cell
https://www.readbyqxmd.com/read/29231137/therapeutic-role-of-harmalol-targeting-nucleic-acids-biophysical-perspective-and-in-vitro-cytotoxicity
#14
Sarita Sarkar, Kakali Bhadra
BACKGROUND: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is growing interest in search for anti-cancer drugs of plant origin with high efficacy, low toxicity and minimum side effects. Most of the chemotherapeutic agents due to their non-selective nature and dose limiting toxicity, use is often restricted, necessitating search for newer drugs having greater potentiality. OBJECTIVE: The review highlighted the interaction of harmalol with nucleic acids of different motifs as sole target biomolecules and in vitro cytotoxicity of the alkaloid in human cancer cell lines with special emphasis on its apoptotic induction ability...
December 11, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29215703/design-synthesis-and-characterization-of-%C3%AE-%C3%AE-unsaturated-carboxylic-acid-and-its-urea-based-derivatives-that-explores-novel-epigenetic-modulators-in-human-non-small-cell-lung-cancer-a549-cell-line
#15
Anusha Chidambaram, S H Kavya, Ramesh Kumar Chidambaram, Rajasekaran Subbiah, John Marshal Jayaraj, Karthikeyan Muthusamy, Ravikumar Vilwanathan
Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against HDAC enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity. On the basis of these observations, we design and synthesize HDAC specific blocker molecules which are specifically besieged towards class I, class II and class IV HDAC isoforms to enhance the structural assortment for HDACi...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29203199/overexpression-of-oct4-induced-by-modulation-of-histone-marks-plays-crucial-role-in-breast-cancer-progression
#16
Swayamsiddha Kar, Samir Kumar Patra
OCT4 is known as the gatekeeper of pluripotent embryonic state as it is responsible for maintenance of pluripotency via self-renewal of embryonic stem cells and acquisition of induced pluripotency via somatic cell reprogramming. OCT4 is responsible for oncogenic transformation by disrupting pre-scheduled differentiation programs and in general, favoring evolution of cancer cells into a more aggressive cancer stem cell phenotype. In this study, we have investigated in details, the epigenetic regulatory mechanisms responsible for over-expression and subsequent aberrant function of OCT4 in breast cancer...
February 15, 2018: Gene
https://www.readbyqxmd.com/read/29192133/synthetic-transcription-elongation-factors-license-transcription-across-repressive-chromatin
#17
Graham S Erwin, Matthew P Grieshop, Asfa Ali, Jun Qi, Matthew Lawlor, Deepak Kumar, Istaq Ahmad, Anna McNally, Natalia Teider, Katie Worringer, Rajeev Sivasankaran, Deeba N Syed, Asuka Eguchi, Md Ashraf, Justin Jeffery, Mousheng Xu, Paul M C Park, Hasan Mukhtar, Achal K Srivastava, Mohammed Faruq, James E Bradner, Aseem Z Ansari
Releasing a paused RNA polymerase II into productive elongation is tightly-regulated, especially at genes that impact human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators...
November 30, 2017: Science
https://www.readbyqxmd.com/read/29181276/i-atac-interactive-pipeline-for-the-management-and-pre-processing-of-atac-seq-samples
#18
Zeeshan Ahmed, Duygu Ucar
Assay for Transposase Accessible Chromatin (ATAC-seq) is an open chromatin profiling assay that is adapted to interrogate chromatin accessibility from small cell numbers. ATAC-seq surmounted a major technical barrier and enabled epigenome profiling of clinical samples. With this advancement in technology, we are now accumulating ATAC-seq samples from clinical samples at an unprecedented rate. These epigenomic profiles hold the key to uncovering how transcriptional programs are established in diverse human cells and are disrupted by genetic or environmental factors...
2017: PeerJ
https://www.readbyqxmd.com/read/29181194/physiological-roles-of-dna-double-strand-breaks
#19
REVIEW
Farhaan A Khan, Syed O Ali
Genomic integrity is constantly threatened by sources of DNA damage, internal and external alike. Among the most cytotoxic lesions is the DNA double-strand break (DSB) which arises from the cleavage of both strands of the double helix. Cells boast a considerable set of defences to both prevent and repair these breaks and drugs which derail these processes represent an important category of anticancer therapeutics. And yet, bizarrely, cells deploy this very machinery for the intentional and calculated disruption of genomic integrity, harnessing potentially destructive DSBs in delicate genetic transactions...
2017: Journal of Nucleic Acids
https://www.readbyqxmd.com/read/29178831/software-for-rapid-time-dependent-chip-sequencing-analysis-tdca
#20
Mike Myschyshyn, Marco Farren-Dai, Tien-Jui Chuang, David Vocadlo
BACKGROUND: Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and associated methods are widely used to define the genome wide distribution of chromatin associated proteins, post-translational epigenetic marks, and modifications found on DNA bases. An area of emerging interest is to study time dependent changes in the distribution of such proteins and marks by using serial ChIP-seq experiments performed in a time resolved manner. Despite such time resolved studies becoming increasingly common, software to facilitate analysis of such data in a robust automated manner is limited...
November 25, 2017: BMC Bioinformatics
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