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Designer chromatin

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https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#1
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28404792/toxoplasma-effectors-targeting-host-signaling-and-transcription
#2
REVIEW
Mohamed-Ali Hakimi, Philipp Olias, L David Sibley
Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions...
July 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28399532/metastatic-pituitary-carcinoma-to-cervical-lymph-node-diagnosis-by-fine-needle-aspiration-and-review-of-the-literature
#3
Huiying Wang, Jiancong Liang, William H Yong, Peggy Sullivan
BACKGROUND: Pituitary carcinomas are rare neoplasms whose designation requires demonstration of metastatic disease. No specific morphologic features can reliably distinguish pituitary carcinomas from pituitary adenomas, rendering the diagnosis particularly challenging. Furthermore, as reports of pituitary carcinoma on fine needle aspiration (FNA) biopsy are exceedingly rare in the literature, the cytological features of pituitary carcinoma are poorly characterized. CASE REPORT: Here we describe a case of pituitary carcinoma in a 67-year-old woman with history of recurrent adrenocorticotropic hormone (ACTH)-producing pituitary adenoma who presented with a persistent left cervical nodule for 2 years...
April 12, 2017: Acta Cytologica
https://www.readbyqxmd.com/read/28398344/induction-of-functional-dopamine-neurons-from-human-astrocytes-in-vitro-and-mouse-astrocytes-in-a-parkinson-s-disease-model
#4
Pia Rivetti di Val Cervo, Roman A Romanov, Giada Spigolon, Débora Masini, Elisa Martín-Montañez, Enrique M Toledo, Gioele La Manno, Michael Feyder, Christian Pifl, Yi-Han Ng, Sara Padrell Sánchez, Sten Linnarsson, Marius Wernig, Tibor Harkany, Gilberto Fisone, Ernest Arenas
Cell replacement therapies for neurodegenerative disease have focused on transplantation of the cell types affected by the pathological process. Here we describe an alternative strategy for Parkinson's disease in which dopamine neurons are generated by direct conversion of astrocytes. Using three transcription factors, NEUROD1, ASCL1 and LMX1A, and the microRNA miR218, collectively designated NeAL218, we reprogram human astrocytes in vitro, and mouse astrocytes in vivo, into induced dopamine neurons (iDANs)...
April 10, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28369277/genogam-genome-wide-generalized-additive-models-for-chip-seq-analysis
#5
Georg Stricker, Alexander Engelhardt, Daniel Schulz, Matthias Schmid, Achim Tresch, Julien Gagneur
Motivation: Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) is a widely used approach to study protein-DNA interactions. Often, the quantities of interest are the differential occupancies relative to controls, between genetic backgrounds, treatments, or combinations thereof. Current methods for differential occupancy of ChIP-seq data rely however on binning or sliding window techniques, for which the choice of the window and bin sizes are subjective. Results: Here, we present GenoGAM (Genome-wide Generalized Additive Model), which brings the well-established and flexible generalized additive models framework to genomic applications using a data parallelism strategy...
March 22, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28359304/determination-of-the-cell-permissiveness-spectrum-mode-of-rna-replication-and-rna-protein-interaction-of-zika-virus
#6
Wangheng Hou, Najealicka Armstrong, Lilian Akello Obwolo, Michael Thomas, Xiaowu Pang, Kevin S Jones, Qiyi Tang
BACKGROUND: Two lineages of Zika virus (ZIKV) have been classified according to the phylogenetic analysis: African and Asian lineages. It is unclear whether differences exist between the two strains in host cell permissiveness, this information is important for understanding viral pathogenesis and designing anti-viral strategies. METHODS: In the present study, we comparatively studied the permissive spectrum of human cells for both the African (MR766) and Asian strains (PRVABC59) using an RNA in situ hybridization (RISH) to visualize RNA replication, an immunofluorescence technology, and a western blot assay to determine viral protein production, and a real-time RT-PCR to examine viral RNA multiplication level...
March 31, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28358847/alpha-1-antitrypsin-suppresses-oxidative-stress-in-preeclampsia-by-inhibiting-the-p38mapk-signaling-pathway-an-in-vivo-and-in-vitro-study
#7
Ya-Ling Feng, Yong-Xiang Yin, Jian Ding, Hua Yuan, Lan Yang, Jian-Juan Xu, Ling-Qin Hu
This present study was designed to investigate the effects of alpha-1-antitrypsin (AAT) on oxidative stress in preeclampsia (PE) by regulating p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. HTR8/SVneo cells were randomly assigned into normal, hypoxia/reoxygenation (H/R), HR + AAT and HR + siRNA-AAT groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expressions of p-p38MAPK, AAT, signal transducer and activator of transcription 1 (STAT1) and activating transcription factor2 (ATF2)...
2017: PloS One
https://www.readbyqxmd.com/read/28341774/rna-dna-hybrid-r-loop-immunoprecipitation-mapping-an-analytical-workflow-to-evaluate-inherent-biases
#8
László Halász, Zsolt Karányi, Beáta Boros-Oláh, Tímea Rózsa, Éva Sipos, Éva Nagy, Ágnes Mosolygó-L, Anett Mázló, Éva Rajnavölgyi, Gábor Halmos, Lóránt Székvölgyi
The impact of R-loops on the physiology and pathology of chromosomes has been demonstrated extensively by chromatin biology research. The progress in this field has been driven by technological advancement of R-loop mapping methods that largely relied on a single approach, DNA-RNA immunoprecipitation (DRIP). Most of the DRIP protocols use the experimental design that was developed by a few laboratories, without paying attention to the potential caveats that might affect the outcome of RNA-DNA hybrid mapping...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28336073/visualization-of-the-genomic-loci-that-are-bound-by-specific-multiprotein-complexes-by-bimolecular-fluorescence-complementation-analysis-on-drosophila-polytene-chromosomes
#9
Huai Deng, Tom K Kerppola
We have developed a procedure that enables visualization of the genomic loci that are bound by complexes formed by a specific combination of chromatin-binding proteins. This procedure is based on imaging bimolecular fluorescence complementation (BiFC) complexes on Drosophila polytene chromosomes. BiFC complexes are formed by the facilitated association of two fluorescent protein fragments that are fused to proteins that interact with, or are in close proximity to, each other. The intensity of BiFC complex fluorescence at individual genomic loci is greatly enhanced by the parallel alignment of hundreds of chromatids within the polytene chromosomes...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28329687/impact-of-dietary-interventions-on-noncoding-rna-networks-and-mrnas-encoding-chromatin-related-factors
#10
Christopher D Green, Yi Huang, Xiaoyang Dou, Liu Yang, Yong Liu, Jing-Dong J Han
Dietary interventions dramatically affect metabolic disease and lifespan in various aging models. Here, we profiled liver microRNA (miRNA), coding, and long non-coding RNA (lncRNA) expression by high-throughput deep sequencing in mice across multiple energy intake and expenditure interventions. Strikingly, three dietary intervention network design patterns were uncovered: (1) lifespan-extending interventions largely repressed the expression of miRNAs, lncRNAs, and transposable elements; (2) protein-coding mRNAs with expression positively correlated with long lifespan are highly targeted by miRNAs; and (3) miRNA-targeting interactions mainly target chromatin-related functions...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329645/frequent-somatic-mutations-of-chromatin-remodeling-genes-in-metastatic-cutaneous-squamous-cell-carcinoma
#11
Amanda Ewart Toland
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 is typically correlated with high survival rates and low rates of metastasis. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals are estimated to die yearly from this disease. As it is difficult to predict which cSCCs are more likely to metastasize, and because there are no targeted therapies specifically designated for metastatic cSCC, we performed exome and targeted sequencing of 18 metastatic and 10 primary cSCCs to identify mutations with potential therapeutic benefit...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28317902/a-natural-tandem-array-alleviates-epigenetic-repression-of-ipa1-and-leads-to-superior-yielding-rice
#12
Lin Zhang, Hong Yu, Bin Ma, Guifu Liu, Jianjun Wang, Junmin Wang, Rongcun Gao, Jinjun Li, Jiyun Liu, Jing Xu, Yingying Zhang, Qun Li, Xuehui Huang, Jianlong Xu, Jianming Li, Qian Qian, Bin Han, Zuhua He, Jiayang Li
Super hybrid rice varieties with ideal plant architecture (IPA) have been critical in enhancing food security worldwide. However, the molecular mechanisms underlying their improved yield remain unclear. Here, we report the identification of a QTL, qWS8/ipa1-2D, in the super rice Yongyou12 (YY12) and related varieties. In-depth genetic molecular characterization of qWS8/ipa1-2D reveals that this newly identified QTL results from three distal naturally occurring tandem repeats upstream of IPA1, a key gene/locus previously shown to shape rice ideal plant architecture and greatly enhance grain yield...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28316324/spatial-organization-of-dna-sequences-directs-the-assembly-of-bacterial-chromatin-by-a-nucleoid-associated-protein
#13
Aleksandre Japaridze, Sylvain Renevey, Patrick Sobetzko, Liubov Stoliar, William Nasser, Giovanni Dietler, Georgi Muskhelishvili
Structural differentiation of bacterial chromatin depends on cooperative binding of abundant nucleoid-associated proteins at numerous genomic DNA sites and stabilization of distinct long-range nucleoprotein structures. Histone-like nucleoid-structuring protein (H-NS) is an abundant DNA-bridging, nucleoid-associated protein that binds to an AT rich conserved DNA sequence motif and regulates both the shape and the genetic expression of the bacterial chromosome. Although there is ample evidence that the mode of H-NS binding depends on environmental conditions, the role of the spatial organization of H-NS binding sequences in the assembly of long-range nucleoprotein structures remains unknown...
March 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301528/genome-wide-mapping-of-histone-h3k9me2-in-acute-myeloid-leukemia-reveals-large-chromosomal-domains-associated-with-massive-gene-silencing-and-sites-of-genome-instability
#14
Anna C Salzberg, Abigail Harris-Becker, Evgenya Y Popova, Nikki Keasey, Thomas P Loughran, David F Claxton, Sergei A Grigoryev
A facultative heterochromatin mark, histone H3 lysine 9 dimethylation (H3K9me2), which is mediated by histone methyltransferases G9a/GLP (EHMT2/1), undergoes dramatic rearrangements during myeloid cell differentiation as observed by chromatin imaging. To determine whether these structural transitions also involve genomic repositioning of H3K9me2, we used ChIP-sequencing to map genome-wide topography of H3K9me2 in normal human granulocytes, normal CD34+ hematopoietic progenitors, primary myeloblasts from acute myeloid leukemia (AML) patients, and a model leukemia cell line K562...
2017: PloS One
https://www.readbyqxmd.com/read/28290446/live-cell-imaging-of-low-and-non-repetitive-chromosome-loci-using-crispr-cas9
#15
Peiwu Qin, Mahmut Parlak, Cem Kuscu, Jigar Bandaria, Mustafa Mir, Karol Szlachta, Ritambhara Singh, Xavier Darzacq, Ahmet Yildiz, Mazhar Adli
Imaging chromatin dynamics is crucial to understand genome organization and its role in transcriptional regulation. Recently, the RNA-guidable feature of CRISPR-Cas9 has been utilized for imaging of chromatin within live cells. However, these methods are mostly applicable to highly repetitive regions, whereas imaging regions with low or no repeats remains as a challenge. To address this challenge, we design single-guide RNAs (sgRNAs) integrated with up to 16 MS2 binding motifs to enable robust fluorescent signal amplification...
March 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28277979/structural-insight-into-inhibitors-of-flavin-adenine-dinucleotide-dependent-lysine-demethylases
#16
Hideaki Niwa, Takashi Umehara
Until 2004, many researchers believed that protein methylation in eukaryotic cells was an irreversible reaction. However, the discovery of lysine-specific demethylase 1 in 2004 drastically changed this view and the concept of chromatin regulation. Since then, the enzymes responsible for lysine demethylation and their cellular substrates, biological significance, and selective regulation have become major research topics in epigenetics and chromatin biology. Many cell-permeable inhibitors for lysine demethylases have been developed, including both target-specific and nonspecific inhibitors...
February 10, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28265266/helz2-is-an-ifn-effector-mediating-suppression-of-dengue-virus
#17
Dahlene N Fusco, Henry Pratt, Stephen Kandilas, Scarlett Se Yun Cheon, Wenyu Lin, D Alex Cronkite, Megha Basavappa, Kate L Jeffrey, Anthony Anselmo, Ruslan Sadreyev, Clarence Yapp, Xu Shi, John F O'Sullivan, Robert E Gerszten, Takuya Tomaru, Satoshi Yoshino, Tetsurou Satoh, Raymond T Chung
Flaviviral infections including dengue virus are an increasing clinical problem worldwide. Dengue infection triggers host production of the type 1 IFN, IFN alpha, one of the strongest and broadest acting antivirals known. However, dengue virus subverts host IFN signaling at early steps of IFN signal transduction. This subversion allows unbridled viral replication which subsequently triggers ongoing production of IFN which, again, is subverted. Identification of downstream IFN antiviral effectors will provide targets which could be activated to restore broad acting antiviral activity, stopping the signal to produce endogenous IFN at toxic levels...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28263745/exercise-increases-hyper-acetylation-of-histones-on-the-cis-element-of-nrf-1-binding-to-the-mef2a-promoter-implications-on-type-2-diabetes
#18
Jitcy S Joseph, Ademola O Ayeleso, Emmanuel Mukwevho
Exercise brings changes on the chromatin ensuing the upregulation of many genes that confer protection from type 2 diabetes. In type-2 diabetes, critical genes are down-regulated such as those involved in glucose transport (GLUT4, MEF2A) and also oxidative phosphorylation (NRF-1 and its target genes). Recent reports have shown that NRF-1 not only regulate mitochondrial oxidative genes but also controls MEF2A, the main transcription factor for glucose transporter, GLUT4. Such dual control of the two pathways by NRF-1 place it as critical gene in the design of therapeutic modalities much needed to cure or better manage type 2 diabetes...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28251877/genomic-landscape-of-cpg-rich-elements-in-human
#19
Vladimir N Babenko, Irina V Chadaeva, Yuriy L Orlov
BACKGROUND: The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location...
February 7, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28240169/epigenetic-modulation-using-small-molecules-targeting-histone-acetyltransferases-in-disease
#20
André Richters, Angela N Koehler
Histone acetyltransferases (HATs) are epigenetic drivers that catalyze the acetyl transfer from acetyl-CoA to lysines of both histone and non-histone substrates and thereby induce transcription either by chromatin remodeling or direct transcription factor activation. Histone deacetylases (HDACs) conduct the reverse reaction to counter HAT activity. Physiological processes such as cell cycle progression or apoptosis require a thoroughly balanced equilibrium of the interplay between acetylation and deacetylation processes to maintain or, if required, alter the global acetylome status...
February 23, 2017: Current Medicinal Chemistry
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