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https://www.readbyqxmd.com/read/28916515/reversing-thyroid-hormone-mediated-repression-of-a-hsv-1-promoter-via-computationally-guided-mutagenesis
#1
Robert W Figliozzi, Feng Chen, Shaochung V Hsia
Thyroid hormones (TH or T3) and their DNA binding nuclear receptors (TRs), direct transcriptional regulation in diverse ways depending on the host cell environment and specific promoter characteristics of TH sensitive genes. This study sought to elucidate the impact on transcriptional repression of nucleotide sequence/orientation within TR binding sites, TR elements, (TREs) of TH sensitive promoters, to better understand ligand dependent transcriptional repression of wild-type promoters. Computational analysis of the HSV-1 thymidine kinase (TK) gene TRE bound by TR and RXR revealed a single TRE point mutation sufficient to reverse the TRE orientation...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28915553/identification-of-a-novel-p53-target-col17a1-that-inhibits-breast-cancer-cell-migration-and-invasion
#2
Varalee Yodsurang, Chizu Tanikawa, Takafumi Miyamoto, Paulisally Hau Yi Lo, Makoto Hirata, Koichi Matsuda
p53 mutation is a marker of poor prognosis in breast cancers. To identify downstream targets of p53, we screened two transcriptome datasets, including cDNA microarrays of MCF10A breast epithelial cells with wild-type p53 or p53-null background, and RNA sequence analysis of breast invasive carcinoma. Here, we unveil ten novel p53 target candidates that are up-regulated after the induction of p53 in wild-type cells. Their expressions are also high in breast invasive carcinoma tissues with wild-type p53. The GO analysis identified epidermis development and ectoderm development, which COL17A1 participates, as significantly up-regulated by wild-type p53...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911122/data-exploration-quality-control-and-statistical-analysis-of-chip-exo-nexus-experiments
#3
Rene Welch, Dongjun Chung, Jeffrey Grass, Robert Landick, Sündüz Keles
ChIP-exo/nexus experiments rely on innovative modifications of the commonly used ChIP-seq protocol for high resolution mapping of transcription factor binding sites. Although many aspects of the ChIP-exo data analysis are similar to those of ChIP-seq, these high throughput experiments pose a number of unique quality control and analysis challenges. We develop a novel statistical quality control pipeline and accompanying R/Bioconductor package, ChIPexoQual, to enable exploration and analysis of ChIP-exo and related experiments...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28904385/rapid-discovery-of-de-novo-deleterious-mutations-in-cattle-enhances-the-value-of-livestock-as-model-species
#4
E Bourneuf, P Otz, H Pausch, V Jagannathan, P Michot, C Grohs, G Piton, S Ammermüller, M-C Deloche, S Fritz, H Leclerc, C Péchoux, A Boukadiri, C Hozé, R Saintilan, F Créchet, M Mosca, D Segelke, F Guillaume, S Bouet, A Baur, A Vasilescu, L Genestout, A Thomas, A Allais-Bonnet, D Rocha, M-A Colle, C Klopp, D Esquerré, C Wurmser, K Flisikowski, H Schwarzenbacher, J Burgstaller, M Brügmann, E Dietschi, N Rudolph, M Freick, S Barbey, G Fayolle, C Danchin-Burge, L Schibler, B Bed'Hom, B J Hayes, H D Daetwyler, R Fries, D Boichard, D Pin, C Drögemüller, A Capitan
In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903905/the-pathogenicity-of-genomic-genetic-variant-of-x-chromosomal-genes-in-males-with-intellectual-disability
#5
Ji-Ping Peng, Fang Liu, Hua Xie, Xiao-Li Chen
Intellectual Disability (ID, previously named mental retardation) is a group of common pediatric neurology disorders characterized by extensive genetic and phenotypic heterogeneity. About 25%-50% of ID was caused by genomic/genetic variants, in which genomic/genetic variants of X-chromosome are one of key pathogenic causation (25%-30%), resulting in X-linked ID (XLID). The epidemiological data showed that the male to female ratio is 1.3: 1 in ID patients. The prevalence of XLID in the whole ID population is 10%-15%, and this prevalence reaches 20%-25% in the male ID population...
June 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28903899/the-application-of-next-generation-sequencing-techniques-in-studying-transcriptional-regulation-in-embryonic-stem-cells
#6
Ya-Jun Liu, Feng Zhang, Hong-de Liu, Xiao Sun
The mechanism of transcriptional regulation has been the focus of many studies in the post-genomic era. The development of sequencing-based technologies for chromatin profiling enables current researchers to experimentally measure chromatin properties. Moreover, many studies aim at annotating the state of the chromatin into broad categories based on observed chromatin features and/or DNA sequences, then associating the resultant distal regulatory regions with the correct target genes based on DNA sequences, and predicting the dependence of epigenetic features on genetic variation...
August 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28903735/foxp3-is-a-hcc-suppressor-gene-and-acts-through-regulating-the-tgf-%C3%AE-smad2-3-signaling-pathway
#7
Jie-Yi Shi, Li-Jie Ma, Ji-Wei Zhang, Meng Duan, Zhen-Bin Ding, Liu-Xiao Yang, Ya Cao, Jian Zhou, Jia Fan, Xiaoming Zhang, Ying-Jun Zhao, Xiao-Ying Wang, Qiang Gao
BACKGROUND: FOXP3 has been discovered to be expressed in tumor cells and participate in the regulation of tumor behavior. Herein, we investigated the clinical relevance and biological significance of FOXP3 expression in human hepatocellular carcinoma (HCC). METHODS: Expression profile of FOXP3 was analyzed using real-time RT-PCR, western blotting and immunofluorescence on HCC cell lines, and immunostaing of a tissue microarray containing of 240 primary HCC samples...
September 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28903418/histone-modification-alteration-coordinated-with-acquisition-of-promoter-dna-methylation-during-epstein-barr-virus-infection
#8
Sayaka Funata, Keisuke Matsusaka, Ryota Yamanaka, Shogo Yamamoto, Atsushi Okabe, Masaki Fukuyo, Hiroyuki Aburatani, Masashi Fukayama, Atsushi Kaneda
Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7. Among 7,775 genes with increased DNA methylation in promoter regions, roughly half were "DNA methylation-sensitive" genes, which acquired DNA methylation in the whole promoter regions and thus were repressed...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28891464/concentration-dependent-chromatin-states-induced-by-the-bicoid-morphogen-gradient
#9
Colleen E Hannon, Shelby A Blythe, Eric F Wieschaus
In Drosophila, graded expression of the maternal transcription factor Bicoid (Bcd) provides positional information to activate target genes at different positions along the anterior-posterior axis. We have measured the genome-wide binding profile of Bcd using ChIP-seq in embryos expressing single, uniform levels of Bcd protein, and grouped Bcd-bound targets into four classes based on occupancy at different concentrations. By measuring the biochemical affinity of target enhancers in these classes in vitro and genome-wide chromatin accessibility by ATAC-seq, we found that the occupancy of target sequences by Bcd is not primarily determined by Bcd binding sites, but by chromatin context...
September 11, 2017: ELife
https://www.readbyqxmd.com/read/28890397/regulated-expression-of-the-tp%C3%AE-isoform-of-the-human-t-prostanoid-receptor-by-the-tumour-suppressors-foxp1-and-nkx3-1-implications-for-the-role-of-thromboxane-in-prostate-cancer
#10
Aine G O'Sullivan, Sarah B Eivers, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX)A2 signals through the TPα and TPβ isoforms of T Prostanoid receptor (TP) that are transcriptionally regulated by distinct promoters termed Prm1 and Prm3, respectively, within the TBXA2R gene. We recently demonstrated that expression of TPα and TPβ is increased in PCa, differentially correlating with Gleason grade and with altered CpG methylation of the individual Prm1/Prm3 regions within the TBXA2R. The current study sought to localise the sites of CpG methylation within Prm1 and Prm3, and to identify the main transcription factors regulating TPβ expression through Prm3 in the prostate adenocarcinoma PC-3 and LNCaP cell lines...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28887473/complete-sequence-based-pathway-analysis-by-differential-on-chip-dna-and-rna-extraction-from-a-single-cell
#11
D van Strijp, R C M Vulders, N A Larsen, J Schira, L Baerlocher, M A van Driel, M Pødenphant, T S Hansen, A Kristensen, K U Mir, T Olesen, W F J Verhaegh, R Marie, P J van der Zaag
We demonstrate on-chip, differential DNA and RNA extraction from a single cell using a microfluidic chip and a two-stage lysis protocol. This method enables direct use of the whole extract, without additional washing steps, reducing sample loss. Using this method, the tumor driving pathway in individual cells from a colorectal cancer cell line was determined by applying a Bayesian computational pathway model to sequences obtained from the RNA fraction of a single cell and, the mutations driving the pathway were determined by analyzing sequences obtained from the DNA fraction of the same single cell...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887412/enzymatic-modules-of-the-saga-chromatin-modifying-complex-play-distinct-roles-in-drosophila-gene-expression-and-development
#12
Xuanying Li, Christopher W Seidel, Leanne T Szerszen, Jeffrey J Lange, Jerry L Workman, Susan M Abmayr
The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not...
September 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28885181/chip-seq-a-powerful-tool-for-studying-protein-dna-interactions-in-plants
#13
Xifeng Chen, Vijai Bhadauria, Bojun Ma
DNA-binding proteins, including transcription factors, epigenetic and chromatin modifiers, control gene expressions in plants. To pinpoint the binding sits of DNA-binding proteins in genome is crucial for decoding gene regulatory networks. Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-Seq) is a widely used approach to identify the DNA regions bound by a specific protein in vivo. The information generated from ChIP-Seq has tremendously advanced our understanding on the mechanism of transcription factors, cofactors and histone modifications in regulating gene expression...
September 8, 2017: Current Issues in Molecular Biology
https://www.readbyqxmd.com/read/28884170/sers-active-metal-dielectric-nanostructures-integrated-in-microfluidic-devices-for-label-free-quantitative-detection-of-mirna
#14
Chiara Novara, Alessandro Chiadò, Niccolò Paccotti, Silvia Catuogno, Carla Lucia Esposito, Gerolama Condorelli, Vittorio De Franciscis, Francesco Geobaldo, Paola Rivolo, Fabrizio Giorgis
In this work, SERS-based microfluidic PDMS chips integrating silver-coated porous silicon membranes were used for the detection and quantitation of microRNAs (miRNAs), which consist of short regulatory non-coding RNA sequences typically over- or under-expressed in connection with several diseases such as oncogenesis. In detail, metal-dielectric nanostructures which provide noticeable Raman enhancements were functionalized according to a biological protocol, adapted and optimized from an enzyme-linked immunosorbent assay (ELISA), for the detection of miR-222...
September 8, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/28882451/development-and-mechanism-of-small-activating-rna-targeting-cebpa-a-novel-therapeutic-in-clinical-trials-for-liver-cancer
#15
Jon Voutila, Vikash Reebye, Thomas C Roberts, Pantelitsa Protopapa, Pinelopi Andrikakou, David C Blakey, Robert Habib, Hans Huber, Pal Saetrom, John J Rossi, Nagy A Habib
Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells...
August 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28881977/denoising-genome-wide-histone-chip-seq-with-convolutional-neural-networks
#16
Pang Wei Koh, Emma Pierson, Anshul Kundaje
Motivation: Chromatin immune-precipitation sequencing (ChIP-seq) experiments are commonly used to obtain genome-wide profiles of histone modifications associated with different types of functional genomic elements. However, the quality of histone ChIP-seq data is affected by many experimental parameters such as the amount of input DNA, antibody specificity, ChIP enrichment and sequencing depth. Making accurate inferences from chromatin profiling experiments that involve diverse experimental parameters is challenging...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28879724/ugt1a1-gene-polymorphism-predicts-irinotecan-induced-severe-neutropenia-and-diarrhea-in-chinese-cancer-patients
#17
Hongwei Peng, Zhouping Duan, Decheng Pan, Jinhua Wen, Xiaohua Wei
BACKGROUND: Irinotecan was widely used in colon cancer and lung cancer, etc., and adverse reactions occur some times. The primary aim of this research is to investigate the association between UGT1A1 gene polymorphisms and irinotecan-related adverse effect in Chinese Han population with a novel kind of gene chip technology. METHODS: UGT1A1*6/*28 gene polymorphisms were detected by PCR and gene chip as well as sequencing. The correlation between UGT1A1 gene polymorphisms and severe delayed diarrhea or neutropenia and effect on response rate and progression-free survival were analyzed...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28878789/effect-of-co-segregating-markers-on-high-density-genetic-maps-and-prediction-of-map-expansion-using-machine-learning-algorithms
#18
Amidou N'Diaye, Jemanesh K Haile, D Brian Fowler, Karim Ammar, Curtis J Pozniak
Advances in sequencing and genotyping methods have enable cost-effective production of high throughput single nucleotide polymorphism (SNP) markers, making them the choice for linkage mapping. As a result, many laboratories have developed high-throughput SNP assays and built high-density genetic maps. However, the number of markers may, by orders of magnitude, exceed the resolution of recombination for a given population size so that only a minority of markers can accurately be ordered. Another issue attached to the so-called 'large p, small n' problem is that high-density genetic maps inevitably result in many markers clustering at the same position (co-segregating markers)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28874528/ein2-mediates-direct-regulation-of-histone-acetylation-in-the-ethylene-response
#19
Fan Zhang, Likai Wang, Bin Qi, Bo Zhao, Eun Esther Ko, Nathaniel D Riggan, Kevin Chin, Hong Qiao
Ethylene gas is essential for developmental processes and stress responses in plants. Although the membrane-bound protein EIN2 is critical for ethylene signaling, the mechanism by which the ethylene signal is transduced remains largely unknown. Here we show the levels of H3K14Ac and H3K23Ac are correlated with the levels of EIN2 protein and demonstrate EIN2 C terminus (EIN2-C) is sufficient to rescue the levels of H3K14/23Ac of ein2-5 at the target loci, using CRISPR/dCas9-EIN2-C. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) and ChIP-reChIP-seq analyses revealed that EIN2-C associates with histone partially through an interaction with EIN2 nuclear-associated protein1 (ENAP1), which preferentially binds to the genome regions that are associated with actively expressed genes both with and without ethylene treatments...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28872116/chromatin-immunoprecipitation-chip-protocol-for-low-abundance-embryonic-samples
#20
Rizwan Rehimi, Michaela Bartusel, Francesca Solinas, Janine Altmüller, Alvaro Rada-Iglesias
Chromatin immunoprecipitation (ChIP) is a widely-used technique for mapping the localization of post-translationally modified histones, histone variants, transcription factors, or chromatin-modifying enzymes at a given locus or on a genome-wide scale. The combination of ChIP assays with next-generation sequencing (i.e., ChIP-Seq) is a powerful approach to globally uncover gene regulatory networks and to improve the functional annotation of genomes, especially of non-coding regulatory sequences. ChIP protocols normally require large amounts of cellular material, thus precluding the applicability of this method to investigating rare cell types or small tissue biopsies...
August 29, 2017: Journal of Visualized Experiments: JoVE
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