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https://www.readbyqxmd.com/read/27913583/epigenetic-control-of-microsomal-prostaglandin-e-synthase-1-by-hdac-mediated-recruitment-of-p300
#1
Christian Fork, Andrea E Vasconez, Patrick Janetzko, Carlo Angioni, Yannick Schreiber, Nerea Ferreiros, Gerd Geisslinger, Matthias S Leisegang, Dieter Steinhilber, Ralf P Brandes
: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medicine to treat pain, fever, inflammation and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. Inhibition of HDACs (HDACi) with the pan HDAC inhibitor SAHA attenuated prostaglandin E2 (PGE2) generation in the murine vasculature and in human vascular smooth muscle cells...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27912097/lncpress1-is-a-p53-regulated-lncrna-that-safeguards-pluripotency-by-disrupting-sirt6-mediated-de-acetylation-of-histone-h3k56
#2
Abhinav K Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C Akdemir, Lalit R Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C Barton
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27903974/lncrnas-are-altered-in-lung-squamous-cell-carcinoma-and-lung-adenocarcinoma
#3
Bing Liu, Yifei Chen, Jiong Yang
Long non-coding RNAs (lncRNAs) have been implicated in pathogenesis of various cancers, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). We used cBioPortal to analyze lncRNA alteration frequencies and their ability to predict overall survival (OS) using 504 LUSC and 522 LUAD samples from The Cancer Genome Atlas (TCGA) database. In LUSC, 624 lncRNAs had alteration rates > 1% and 64 > 10%. In LUAD 625 lncRNAs had alteration rates > 1% and 36 > 10%. Among those, 620 lncRNAs had alteration frequencies > 1% in both LUSC and LUAD, while 22 were LUSC-specific and 23 were LUAD-specific...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903901/core-binding-factor-cbf-is-required-for-epstein-barr-virus-ebna3-proteins-to-regulate-target-gene-expression
#4
Kostas Paschos, Quentin Bazot, Guiyi Ho, Gillian A Parker, Jonathan Lees, Geraint Barton, Martin J Allday
ChIP-seq performed on lymphoblastoid cell lines (LCLs), expressing epitope-tagged EBNA3A, EBNA3B or EBNA3C from EBV-recombinants, revealed important principles of EBNA3 binding to chromatin. When combined with global chromatin looping data, EBNA3-bound loci were found to have a singular character, each directly associating with either EBNA3-repressed or EBNA3-activated genes, but not with both. EBNA3A and EBNA3C showed significant association with repressed and activated genes. Significant direct association for EBNA3B loci could only be shown with EBNA3B-repressed genes...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902860/genetic-and-biochemical-interactions-between-the-bacterial-replication-initiator-dnaa-and-the-nucleoid-associated-protein-rok-in-bacillus-subtilis
#5
Charlotte A Seid, Janet L Smith, Alan D Grossman
We identified interactions between the conserved bacterial replication initiator and transcription factor DnaA and the nucleoid-associated protein Rok of Bacillus subtilis. DnaA binds directly to clusters of DnaA boxes at the origin of replication and elsewhere, including the promoters of several DnaA-regulated genes. Rok, an analog of H-NS from gamma-proteobacteria that affects chromosome architecture and Lsr2 from Mycobacteria, binds A+T-rich sequences throughout the genome and represses expression of many genes...
November 30, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27902686/genomic-characterization-of-metformin-hepatic-response
#6
Marcelo R Luizon, Walter L Eckalbar, Yao Wang, Stacy L Jones, Robin P Smith, Megan Laurance, Lawrence Lin, Paul J Gallins, Amy S Etheridge, Fred Wright, Yihui Zhou, Cliona Molony, Federico Innocenti, Sook Wah Yee, Kathleen M Giacomini, Nadav Ahituv
Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27899659/discovery-and-validation-of-information-theory-based-transcription-factor-and-cofactor-binding-site-motifs
#7
Ruipeng Lu, Eliseos J Mucaki, Peter K Rogan
Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899623/combining-transcription-factor-binding-affinities-with-open-chromatin-data-for-accurate-gene-expression-prediction
#8
Florian Schmidt, Nina Gasparoni, Gilles Gasparoni, Kathrin Gianmoena, Cristina Cadenas, Julia K Polansky, Peter Ebert, Karl Nordström, Matthias Barann, Anupam Sinha, Sebastian Fröhler, Jieyi Xiong, Azim Dehghani Amirabad, Fatemeh Behjati Ardakani, Barbara Hutter, Gideon Zipprich, Bärbel Felder, Jürgen Eils, Benedikt Brors, Wei Chen, Jan G Hengstler, Alf Hamann, Thomas Lengauer, Philip Rosenstiel, Jörn Walter, Marcel H Schulz
The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid costly TF ChIP-seq assays. Thus, it is important to develop computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices. TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899603/promiscuous-dna-binding-of-a-mutant-zinc-finger-protein-corrupts-the-transcriptome-and-diminishes-cell-viability
#9
Kevin R Gillinder, Melissa D Ilsley, Danitza Nébor, Ravi Sachidanandam, Mathieu Lajoie, Graham W Magor, Michael R Tallack, Timothy Bailey, Michael J Landsberg, Joel P Mackay, Michael W Parker, Luke A Miles, Joel H Graber, Luanne L Peters, James J Bieker, Andrew C Perkins
The rules of engagement between zinc finger transcription factors and DNA have been partly defined by in vitro DNA-binding and structural studies, but less is known about how these rules apply in vivo Here, we demonstrate how a missense mutation in the second zinc finger of Krüppel-like factor-1 (KLF1) leads to degenerate DNA-binding specificity in vivo, resulting in ectopic transcription and anemia in the Nan mouse model. We employed ChIP-seq and 4sU-RNA-seq to identify aberrant DNA-binding events genome wide and ectopic transcriptional consequences of this binding...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899590/different%C3%A2-enhancer-classes-in-drosophila-bind-distinct-architectural-proteins-and-mediate-unique-chromatin-interactions-and-3d-architecture
#10
Caelin Cubeñas-Potts, M Jordan Rowley, Xiaowen Lyu, Ge Li, Elissa P Lei, Victor G Corces
Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895806/genome-wide-epigenomic-profiling-for-biomarker-discovery
#11
REVIEW
René A M Dirks, Hendrik G Stunnenberg, Hendrik Marks
A myriad of diseases is caused or characterized by alteration of epigenetic patterns, including changes in DNA methylation, post-translational histone modifications, or chromatin structure. These changes of the epigenome represent a highly interesting layer of information for disease stratification and for personalized medicine. Traditionally, epigenomic profiling required large amounts of cells, which are rarely available with clinical samples. Also, the cellular heterogeneity complicates analysis when profiling clinical samples for unbiased genome-wide biomarker discovery...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27893733/adarb1-catalyzes-circadian-a-to-i-editing-and-regulates-rna-rhythm
#12
Hideki Terajima, Hikari Yoshitane, Haruka Ozaki, Yutaka Suzuki, Shigeki Shimba, Shinya Kuroda, Wataru Iwasaki, Yoshitaka Fukada
It has been proposed that the CLOCK-ARNTL (BMAL1) complex drives circadian transcription of thousands of genes, including Per and Cry family genes that encode suppressors of CLOCK-ARNTL-dependent transcription. However, recent studies demonstrated that 70-80% of circadian-oscillating mRNAs have no obvious rhythms in their de novo transcription, indicating the potential importance of post-transcriptional regulation. Our CLOCK-ChIP-seq analysis identified rhythmic expression of adenosine deaminase, RNA-specific, B1 (Adarb1, also known as Adar2), an adenosine-to-inosine (A-to-I) RNA-editing enzyme...
November 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27893398/probabilistic-inference-on-multiple-normalized-genome-wide-signal-profiles-with-model-regularization
#13
Ka-Chun Wong, Chengbin Peng, Shankai Yan, Cheng Liang
Understanding genome-wide protein-DNA interactions forms the basis for further focused studies. In particular, the chromatin immunoprecipitation (ChIP) with sequencing (ChIPSeq) technology can enable us to measure the genome-wide occupancy of DNA-binding protein of interest in vivo. Multiple ChIP-Seq runs thus inherent the potential for us to decipher the combinatorial interactions among multiple DNA-binding proteins. To handle those multiple genome-wide runs, we propose to integrate regularized regression functions (i...
November 21, 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27893179/ctra-controls-cell-division-and-outer-membrane-composition-of-the-pathogen-brucella-abortus
#14
Nayla Francis, Katy Poncin, Antonella Fioravanti, Victoria Vassen, Kevin Willemart, Thi Anh Phuong Ong, Luca Rappez, Jean-Jacques Letesson, Emanuele G Biondi, Xavier De Bolle
Brucella abortus is a pathogen infecting cattle, able to survive, traffic and proliferate inside host cells. It belongs to the Alphaproteobacteria, a phylogenetic group comprising bacteria with free living, symbiotic and pathogenic lifestyles. An essential regulator of cell cycle progression named CtrA was described in the model bacterium Caulobacter crescentus. This regulator is conserved in many alphaproteobacteria, but the evolution of its regulon remains elusive. Here we identified promoters that are CtrA targets using ChIP-seq and we found that CtrA binds to promoters of genes involved in cell cycle progression, in addition to numerous genes encoding outer membrane components involved in export of membrane proteins and synthesis of lipopolysaccharide...
November 28, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27886717/rubioseq-a-multiplatform-application-that-executes-parallelized-pipelines-to-analyse-next-generation-sequencing-data
#15
Miriam Rubio-Camarillo, Hugo López-Fernández, Gonzalo Gómez-López, Ángel Carro, José María Fernández, Coral Fustero Torre, Florentino Fdez-Riverola, Daniel Glez-Peña
BACKGROUND AND OBJECTIVE: To facilitate routine analysis and to improve the reproducibility of the results, next-generation sequencing (NGS) analysis requires intuitive, efficient and integrated data processing pipelines. METHODS: We have selected well-established software to construct a suite of automated and parallelized workflows to analyse NGS data for DNA-seq (single-nucleotide variants (SNVs) and indels), CNA-seq, bisulfite-seq and ChIP-seq experiments. RESULTS: Here, we present RUbioSeq+, an updated and extended version of RUbioSeq, a multiplatform application that incorporates a suite of automated and parallelized workflows to analyse NGS data...
January 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/27886167/mapping-of-long-range-chromatin-interactions-by-proximity-ligation-assisted-chip-seq
#16
Rongxin Fang, Miao Yu, Guoqiang Li, Sora Chee, Tristin Liu, Anthony D Schmitt, Bing Ren
No abstract text is available yet for this article.
December 2016: Cell Research
https://www.readbyqxmd.com/read/27882329/an-entropy-based-position-projection-algorithm-for-motif-discovery
#17
Yipu Zhang, Ping Wang, Maode Yan
Motif discovery problem is crucial for understanding the structure and function of gene expression. Over the past decades, many attempts using consensus and probability training model for motif finding are successful. However, the most existing motif discovery algorithms are still time-consuming or easily trapped in a local optimum. To overcome these shortcomings, in this paper, we propose an entropy-based position projection algorithm, called EPP, which designs a projection process to divide the dataset and explores the best local optimal solution...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27879268/transcriptional-selectivity-of-epigenetic-therapy-in-cancer
#18
Takahiro Sato, Matteo Cesaroni, Woonbok Chung, Shoghag Panjarian, Anthony Tran, Jozef Madzo, Yasuyuki Okamoto, Hanghang Zhang, Xiaowei Chen, Jaroslav Jelinek, Jean-Pierre J Issa
A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation and ChIP-seq analyses the epigenetic response of a set of colon, breast and leukemia cancer cell lines to small molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343)...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27879206/exon-junction-complex-proteins-bind-nascent-transcripts-independently-of-pre-mrna-splicing-in-drosophila-melanogaster
#19
Subhendu Roy Choudhury, Anand K Singh, Tina McLeod, Marco Blanchette, Boyun Jang, Paul Badenhorst, Aditi Kanhere, Saverio Brogna
Although it is currently understood that the exon junction complex (EJC) is recruited on spliced mRNA by a specific interaction between its central protein, eIF4AIII, and splicing factor CWC22, we found that eIF4AIII and the other EJC core proteins Y14 and MAGO bind the nascent transcripts of not only intron-containing but also intronless genes on Drosophila polytene chromosome. Additionally, Y14 ChIP-seq demonstrates that association with transcribed genes is also splicing-independent in Drosophila S2 cells...
November 23, 2016: ELife
https://www.readbyqxmd.com/read/27876826/bgrmi-a-method-for-inferring-gene-regulatory-networks-from-time-course-gene-expression-data-and-its-application-in-breast-cancer-research
#20
Luis F Iglesias-Martinez, Walter Kolch, Tapesh Santra
Reconstructing gene regulatory networks (GRNs) from gene expression data is a challenging problem. Existing GRN reconstruction algorithms can be broadly divided into model-free and model-based methods. Typically, model-free methods have high accuracy but are computation intensive whereas model-based methods are fast but less accurate. We propose Bayesian Gene Regulation Model Inference (BGRMI), a model-based method for inferring GRNs from time-course gene expression data. BGRMI uses a Bayesian framework to calculate the probability of different models of GRNs and a heuristic search strategy to scan the model space efficiently...
November 23, 2016: Scientific Reports
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