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https://www.readbyqxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#1
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28427179/comprehensive-mapping-of-the-effects-of-azacitidine-on-dna-methylation-repressive-permissive-histone-marks-and-gene-expression-in-primary-cells-from-patients-with-mds-and-mds-related-disease
#2
Magnus Tobiasson, Hani Abdulkadir, Andreas Lennartsson, Shintaro Katayama, Francesco Marabita, Ayla De Paepe, Mohsen Karimi, Kaarel Krjutskov, Elisabet Einarsdottir, Michael Grövdal, Monika Jansson, Asmaa Ben Azenkoud, Lina Corddedu, Sören Lehmann, Karl Ekwall, Juha Kere, Eva Hellström-Lindberg, Johanna Ungerstedt
Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423325/rapid-genome-wide-recruitment-of-rna-polymerase-ii-drives-transcription-splicing-and-translation-events-during-t-cell-responses
#3
Kathrin Davari, Johannes Lichti, Christian Gallus, Franziska Greulich, N Henriette Uhlenhaut, Matthias Heinig, Caroline C Friedel, Elke Glasmacher
Activation of immune cells results in rapid functional changes, but how such fast changes are accomplished remains enigmatic. By combining time courses of 4sU-seq, RNA-seq, ribosome profiling (RP), and RNA polymerase II (RNA Pol II) ChIP-seq during T cell activation, we illustrate genome-wide temporal dynamics for ∼10,000 genes. This approach reveals not only immediate-early and posttranscriptionally regulated genes but also coupled changes in transcription and translation for >90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily mediates transcriptional changes...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28420760/novel-lnc-rna-regulated-by-hif-1-inhibits-apoptotic-cell-death-in-the-renal-tubular-epithelial-cells-under-hypoxia
#4
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Natsuki Kushida, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28420675/integrative-analysis-unveils-new-functions-for-the-drosophila-cutoff-protein-in-non-coding-rna-biogenesis-and-gene-regulation
#5
Yuri Pritykin, Tarcisio Brito, Trudi Schupbach, Mona Singh, Attilio Pane
Piwi-Interacting RNAs (piRNAs) are central components of the piRNA pathway, which directs transposon silencing and guarantees genome integrity in the germ cells of several metazoans. In Drosophila, piRNAs are produced from discrete regions of the genome termed piRNA clusters, whose expression relies on the RDC complex comprised of the core proteins Rhino, Deadlock and Cutoff. To date, the RDC complex has been exclusively implicated in the regulation of the piRNA loci. Here we further elucidate the function of Cutoff and the RDC complex by performing genome-wide ChIP-seq and RNA-seq assays in the Drosophila germline and analyzing these data together with other publicly available data sets...
April 18, 2017: RNA
https://www.readbyqxmd.com/read/28416945/a-chip-seq-data-analysis-pipeline-based-on-bioconductor-packages
#6
Seung-Jin Park, Jong-Hwan Kim, Byung-Ha Yoon, Seon-Young Kim
Nowadays, huge volumes of chromatin immunoprecipitation-sequencing (ChIP-Seq) data are generated to increase the knowledge on DNA-protein interactions in the cell, and accordingly, many tools have been developed for ChIP-Seq analysis. Here, we provide an example of a streamlined workflow for ChIP-Seq data analysis composed of only four packages in Bioconductor: dada2, QuasR, mosaics, and ChIPseeker. 'dada2' performs trimming of the high-throughput sequencing data. 'QuasR' and 'mosaics' perform quality control and mapping of the input reads to the reference genome and peak calling, respectively...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28416760/the-histone-demethylase-kdm3a-regulates-the-transcriptional-program-of-the-androgen-receptor-in-prostate-cancer-cells
#7
Stephen Wilson, Lingling Fan, Natasha Sahgal, Jianfei Qi, Fabian V Filipp
The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414715/transcriptional-regulatory-logic-of-the-diurnal-cycle-in-the-mouse-liver
#8
Jonathan Aryeh Sobel, Irina Krier, Teemu Andersin, Sunil Raghav, Donatella Canella, Federica Gilardi, Alexandra Styliani Kalantzi, Guillaume Rey, Benjamin Weger, Frédéric Gachon, Matteo Dal Peraro, Nouria Hernandez, Ueli Schibler, Bart Deplancke, Felix Naef
Many organisms exhibit temporal rhythms in gene expression that propel diurnal cycles in physiology. In the liver of mammals, these rhythms are controlled by transcription-translation feedback loops of the core circadian clock and by feeding-fasting cycles. To better understand the regulatory interplay between the circadian clock and feeding rhythms, we mapped DNase I hypersensitive sites (DHSs) in the mouse liver during a diurnal cycle. The intensity of DNase I cleavages cycled at a substantial fraction of all DHSs, suggesting that DHSs harbor regulatory elements that control rhythmic transcription...
April 2017: PLoS Biology
https://www.readbyqxmd.com/read/28411381/pbx3-is-essential-for-leukemia-stem-cell-maintenance-in-mll-rearranged-leukemia
#9
Huidong Guo, Yajing Chu, Le Wang, Xing Chen, Yangpeng Chen, Hui Cheng, Lei Zhang, Yuan Zhou, Feng-Chun Yang, Tao Cheng, Mingjiang Xu, Xiaobing Zhang, Jianfeng Zhou, Weiping Yuan
Interaction of HOXA9/MEIS1/PBX3 is responsible for hematopoietic system transformation in MLL-rearranged (MLL-r) leukemia. Of these genes, HOXA9 has been shown to be critical for leukemia cell survival, while MEIS1 has been identified as an essential regulator for leukemia stem cell (LSC) maintenance. Although significantly high expression of PBX3 was observed in clinical acute myeloid leukemia (AML) samples, the individual role of PBX3 in leukemia development is still largely unknown. In this study, we explored the specific role of PBX3 and its associated regulatory network in leukemia progression...
April 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28411283/systematic-functional-perturbations-uncover-a-prognostic-genetic-network-driving-human-breast-cancer
#10
Tristan Gallenne, Kenneth N Ross, Nils L Visser, Salony, Christophe J Desmet, Ben S Wittner, Lodewyk F A Wessels, Sridhar Ramaswamy, Daniel S Peeper
Prognostic classifiers conceivably comprise biomarker genes that functionally contribute to the oncogenic and metastatic properties of cancer, but this has not been investigated systematically. The transcription factor Fra-1 not only has an essential role in breast cancer, but also drives the expression of a highly prognostic gene set. Here, we systematically perturbed the function of 31 individual Fra-1-dependent poor-prognosis genes and examined their impact on breast cancer growth in vivo. We find that stable shRNA depletion of each of nine individual signature genes strongly inhibits breast cancer growth and aggressiveness...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406899/histone-deacetylase-inhibition-modulates-histone-acetylation-at-gene-promoter-regions-and-affects-genome-wide-gene-transcription-in-schistosoma-mansoni
#11
Letícia Anderson, Monete Rajão Gomes, Lucas Ferreira daSilva, Adriana da Silva Andrade Pereira, Marina M Mourão, Christophe Romier, Raymond Pierce, Sergio Verjovski-Almeida
BACKGROUND: Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. METHODOLOGY/PRINCIPAL FINDINGS: TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3...
April 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28406749/nucleosome-repositioning-during-differentiation-of-a-human-myeloid-leukemia-cell-line
#12
Vladimir B Teif, Jan-Philipp Mallm, Tanvi Sharma, David B Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L Olins, Donald E Olins
Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope)...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28402957/chromatin-state-dynamics-during-nk-cell-activation
#13
Yang Li, Jin Wang, Jie Yin, Xinhua Liu, Minghang Yu, Ting Li, Han Yan, Xi Wang
Studies of Natural Killer (NK) cell cytotoxicity have mainly focused on the balance of activating and inhibitory receptors, signaling transduction, calcium influx, formation of immune synapse, and cytolytic degranulation. However, little is known about the chromatin state of NK cells and the impact of its changes during target recognition. In this study, we investigate the contribution of chromatin state dynamics during NK cell activation by comprehensively analyzing a set of microarray data and two sets of Chromatin Immunoprecipitation-Sequencing (ChIP-seq) data...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402947/overexpression-of-the-transcription-factor-atf3-with-a-regulatory-molecular-signature-associates-with-the-pathogenic-development-of-colorectal-cancer
#14
Feng Yan, Le Ying, Xiaofang Li, Bin Qiao, Qiaohong Meng, Liang Yu, Xiangliang Yuan, Shu-Ting Ren, David W Chan, Liyun Shi, Peihua Ni, Xuefeng Wang, Dakang Xu, Yiqun Hu
The identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402545/orio-online-resource-for-integrative-omics-a-web-based-platform-for-rapid-integration-of-next-generation-sequencing-data
#15
Christopher A Lavender, Andrew J Shapiro, Adam B Burkholder, Brian D Bennett, Karen Adelman, David C Fargo
Established and emerging next generation sequencing (NGS)-based technologies allow for genome-wide interrogation of diverse biological processes. However, accessibility of NGS data remains a problem, and few user-friendly resources exist for integrative analysis of NGS data from different sources and experimental techniques. Here, we present Online Resource for Integrative Omics (ORIO; https://orio.niehs.nih.gov/), a web-based resource with an intuitive user interface for rapid analysis and integration of NGS data...
April 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28400269/nf-%C3%AE%C2%BAb-controls-four-genes-encoding-core-enzymes-of-tricarboxylic-acid-cycle
#16
Fei Zhou, Xinhui Xu, Jian Wu, Danyang Wang, Jinke Wang
NF-κB may promote tumor progression by altering cell metabolism. Hence, finding its target genes that are involved in cell metabolism is helpful for understanding its role in tumor growth. Here we discovered four metabolism-related target genes of this transcription factor. By analyzing a chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) data that characterizing the global binding sites (BSs) of NF-κB RelA in the TNFα-stimulated HeLa cells, we found that four genes that encode core enzymes of the tricarboxylic acid (TCA) cycle, including IDH1, IDH3A, ACO2, and SUCLA2, were multiply bound by this transcription factor...
April 8, 2017: Gene
https://www.readbyqxmd.com/read/28398543/funchip-an-r-bioconductor-package-for-functional-classification-of-chip-seq-shapes
#17
Alice C L Parodi, Laura M Sangalli, Simone Vantini, Bruno Amati, Piercesare Secchi, Marco J Morelli
Summary: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) generates local accumulations of sequencing reads on the genome ("peaks"), which correspond to specific protein-DNA interactions or chromatin modifications. Peaks are detected by considering their total area above a background signal, usually neglecting their shapes, which instead may convey additional biological information. We present FunChIP, an R/Bioconductor package for clustering peaks according to a functional representation of their shapes: after approximating their profiles with cubic B-splines, FunChIP minimises their functional distance and classifies the peaks applying a k-mean alignment and clustering algorithm...
April 7, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28394262/mutant-p53-establishes-targetable-tumor-dependency-by-promoting-unscheduled-replication
#18
Shilpa Singh, Catherine A Vaughan, Rebecca A Frum, Steven R Grossman, Sumitra Deb, Swati Palit Deb
Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities...
April 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28393877/comprehensive-mapping-of-the-helicobacter-pylori-nikr-regulon-provides-new-insights-in-bacterial-nickel-responses
#19
Andrea Vannini, Eva Pinatel, Paolo Emidio Costantini, Simone Pelliciari, Davide Roncarati, Simone Puccio, Gianluca De Bellis, Clelia Peano, Alberto Danielli
Nickel homeostasis is important for pathogenic and ureolytic bacteria, which use this metal ion as enzymatic cofactor. For example, in the human pathogen Helicobacter pylori an optimal balance between nickel uptake and incorporation in metallo-enzymes is fundamental for colonization of the host. Nickel is also used as cofactor to modulate DNA binding of the NikR regulator, which controls transcription of genes involved in nickel trafficking or infection in many bacteria. Accordingly, there is much interest in a systematic characterization of NikR regulation...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28387974/the-streptomyces-o-b-one-connection-a-force-within-layered-repression-of-a-key-developmental-decision
#20
Klas Flärdh, Joseph R McCormick
The study of Streptomyces development has made significant advances in the past few years and ongoing work is poised to add even more. One key to advancing the field has been the application of genome-wide approaches using S. venezuelae, which is capable of fairly synchronous sporulation in submerged growth conditions. WhiA and WhiB are well-known transcriptional regulators governing the pathway for spore formation in aerial hyphae. Recent ChIP-seq and RNA expression analyses indicated that WhiA and WhiB regulate the same set of genes, each being dependent on the presence of the other to exert control...
April 7, 2017: Molecular Microbiology
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