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https://www.readbyqxmd.com/read/29453291/lsd1-inhibition-exerts-its-anti-leukemic-effect-by-recommissioning-pu-1-and-c-ebp%C3%AE-dependent-enhancers-in-aml
#1
Monica Cusan, Sheng F Cai, Helai P Mohammad, Andrei Krivtsov, Alan Chramiec, Evangelia Loizou, Matthew D Witkin, Kimberly N Smitheman, Daniel G Tenen, Min Ye, Britta Will, Ulrich Steidl, Ryan G Kruger, Ross L Levine, Hugh Y Rienhoff, Richard P Koche, Scott A Armstrong
Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML...
February 16, 2018: Blood
https://www.readbyqxmd.com/read/29449694/interaction-between-stat3-and-gli1-tgli1-oncogenic-transcription-factors-promotes-the-aggressiveness-of-triple-negative-breast-cancers-and-her2-enriched-breast-cancer
#2
Sherona R Sirkisoon, Richard L Carpenter, Tadas Rimkus, Ashley Anderson, Alexandria Harrison, Allison M Lange, Guangxu Jin, Kounosuke Watabe, Hui-Wen Lo
Signal transducer and activator of transcription 3 (STAT3), glioma oncogene homolog 1 (GLI1), and truncated GLI1 (tGLI1) are oncogenic transcription factors playing important roles in breast cancer. tGLI1 is a gain-of-function GLI1 isoform. Whether STAT3 physically and/or functionally interacts with GLI1/tGLI1 has not been explored. To address this knowledge gap, we analyzed 47 node-positive breast cancer specimens using immunohistochemical staining and found that phosphorylated-STAT3 (Y705), GLI1, and tGLI1 are co-overexpressed in the majority of triple-negative breast carcinomas (64%) and HER2-enriched (68%) breast carcinomas, and in lymph node metastases (65%)...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29445148/temporal-requirements-for-isl1-in-sympathetic-neuron-proliferation-differentiation-and-diversification
#3
Qingquan Zhang, Ru Huang, Youqiong Ye, Xiaoxia Guo, Jun Lu, Fugui Zhu, Xiaohui Gong, Qitong Zhang, Jie Yan, Lina Luo, Shaowei Zhuang, Yihan Chen, Xiaodong Zhao, Sylvia M Evans, Cizhong Jiang, Xingqun Liang, Yunfu Sun
Malformations of the sympathetic nervous system have been associated with cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A better understanding of the factors regulating sympathetic nervous system development is critical to the development of potential therapies. Here, we have uncovered a temporal requirement for the LIM homeodomain transcription factor ISL1 during sympathetic nervous system development by the analysis of two mutant mouse lines: an Isl1 hypomorphic line and mice with Isl1 ablated in neural crest lineages...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444334/optimized-methods-of-chromatin-immunoprecipitation-chip-for-profiling-histone-modifications-in-industrial-microalgae-nannochloropsis-spp
#4
Li Wei, Jian Xu
Epigenetic factors such as histone modifications play integral roles in plant development and stress response, yet their implications in algae remain poorly understood. In the industrial oleaginous microalgae Nannochloropsis spp., the lack of an efficient methodology for chromatin immunoprecipitation (ChIP), which determines the specific genomic location of various histone modifications, has hindered probing the epigenetic basis of their photosynthetic carbon conversion and storage as oil. Here, a detailed ChIP protocol was developed for Nannochloropsis oceanica, which represents a reliable approach for the analysis of histone modifications, chromatin state, and transcription factor binding sites at the epigenetic level...
February 14, 2018: Journal of Phycology
https://www.readbyqxmd.com/read/29444131/chromatin-immunoprecipitation-improvements-for-the-processing-of-small-frozen-pieces-of-adipose-tissue
#5
Daniel Castellano-Castillo, Pierre-Damien Denechaud, Isabel Moreno-Indias, Francisco Tinahones, Lluis Fajas, María Isabel Queipo-Ortuño, Fernando Cardona
Chromatin immunoprecipitation (ChIP) has gained importance to identify links between the genome and the proteome. Adipose tissue has emerged as an active tissue, which secretes a wide range of molecules that have been related to metabolic and obesity-related disorders, such as diabetes, cardiovascular failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the importance in discerning the possible relationship between metabolic disorders, lifestyle and environment. However, ChIP application in human adipose tissue is limited by several factors, such as sample size, frozen sample availability, high lipid content and cellular composition of the tissue...
2018: PloS One
https://www.readbyqxmd.com/read/29442330/roles-of-zic2-in-regulation-of-pluripotent-stem-cells
#6
Hisato Kondoh
Pioneered by the classical mouse embryonic stem cells (ESCs), various stem cell lines representing the peri- and postimplantation stages of embryogenesis have been established. To gain insight into the gene regulatory network operating in these cells, we first investigated epiblast stem cells (EpiSCs), performing ChIP-seq analysis for five major transcription factors (TFs) involved in epiblast regulation. The analysis indicated that SOX2-POU5F1 TF pairs highlighted in mouse ESCs are not the major players in other stem cells...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29438720/selenite-and-methylseleninic-acid-epigenetically-affects-distinct-gene-sets-in-myeloid-leukemia-a-genome-wide-epigenetic-analysis
#7
Prajakta Khalkar, Hani Abdulkadir Ali, Paula Codó, Nuria Díaz Argelich, Anni Martikainen, Mohsen Karimi Arzenani, Sören Lehmann, Julian Walfridsson, Johanna Ungerstedt, Aristi P Fernandes
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq)...
February 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29438498/chromswitch-a-flexible-method-to-detect-chromatin-state-switches
#8
Selin Jessa, Claudia L Kleinman, John Hancock
Summary: Chromatin state plays a major role in controlling gene expression, and comparative analysis of ChIP-seq data is key to understanding epigenetic regulation. We present chromswitch, an R/Bioconductor package to integrate epigenomic data in a defined window of interest to detect an overall switch in chromatin state. Chromswitch accurately classifies a benchmarking dataset, and when applied genome-wide, the tool successfully detects chromatin changes that result in brain-specific expression...
February 9, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29438444/systems-genomics-study-reveals-expression-quantitative-trait-loci-regulator-genes-and-pathways-associated-with-boar-taint-in-pigs
#9
Markus Drag, Mathias B Hansen, Haja N Kadarmideen
Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs) with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS) were slaughtered at ~100 kg...
2018: PloS One
https://www.readbyqxmd.com/read/29436476/opaque11-is-a-central-hub-of-the-regulatory-network-for-maize-endosperm-development-and-nutrient-metabolism
#10
Fan Feng, Weiwei Qi, Yuanda Lv, Shumei Yan, Liming Xu, Wenyao Yang, Yue Yuan, Yihan Chen, Han Zhao, Rentao Song
Maize (Zea mays) endosperm is a primary tissue for nutrient storage and is highly differentiated during development. However, the regulatory networks of endosperm development and nutrient metabolism remain largely unknown. Maize opaque11 (o11) is a classic seed mutant with a small and opaque endosperm showing decreased starch and protein accumulation. We cloned O11 and found that it encodes an endosperm-specific bHLH transcription factor (TF). Loss-of-function of O11 significantly affected transcription of carbohydrate/amino acid metabolism and stress-response genes...
February 7, 2018: Plant Cell
https://www.readbyqxmd.com/read/29432416/sox2-regulates-common-and-specific-stem-cell-features-in-the-cns-and-endoderm-derived-organs
#11
Daniel W Hagey, Susanne Klum, Idha Kurtsdotter, Cecile Zaouter, Danijal Topcic, Olov Andersson, Maria Bergsland, Jonas Muhr
Stem cells are defined by their capacities to self-renew and generate progeny of multiple lineages. The transcription factor SOX2 has key roles in the regulation of stem cell characteristics, but whether SOX2 achieves these functions through similar mechanisms in distinct stem cell populations is not known. To address this question, we performed RNA-seq and SOX2 ChIP-seq on embryonic mouse cortex, spinal cord, stomach and lung/esophagus. We demonstrate that, although SOX2 binds a similar motif in the different cell types, its target regions are primarily cell-type-specific and enriched for the distinct binding motifs of appropriately expressed interacting co-factors...
February 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29432187/global-changes-of-h3k27me3-domains-and-polycomb-group-protein-distribution-in-the-absence-of-recruiters-spps-or-pho
#12
J Lesley Brown, Ming-An Sun, Judith A Kassis
Polycomb group (PcG) proteins maintain the silenced state of key developmental genes in animals, but how these proteins are recruited to specific regions of the genome is still poorly understood. In Drosophila , PcG proteins are recruited to Polycomb response elements (PREs) that include combinations of sites for sequence specific DNA binding "PcG recruiters," including Pho, Cg, and Spps. To understand their roles in PcG recruitment, we compared Pho-, Cg-, and Spps-binding sites against H3K27me3 and key PcG proteins by ChIP-seq in wild-type and mutant third instar larvae...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29429977/zfx-acts-as-a-transcriptional-activator-in-multiple-types-of-human-tumors-by-binding-downstream-of-transcription-start-sites-at-the-majority-of-cpg-island-promoters
#13
Suhn Kyong Rhie, Lijun Yao, Zhifei Luo, Heather Witt, Shannon Schreiner, Yu Guo, Andrew A Perez, Peggy J Farnham
High expression of the transcription factor ZFX is correlated with proliferation, tumorigenesis, and patient survival in multiple types of human cancers. However, the mechanism by which ZFX influences transcriptional regulation has not been determined. We performed ChIP-seq in four cancer cell lines (representing kidney, colon, prostate, and breast cancers) to identify ZFX binding sites throughout the human genome. We identified ~9,000 ZFX binding sites and found that the majority of the sites are in CpG island promoters...
February 2, 2018: Genome Research
https://www.readbyqxmd.com/read/29429127/tissue-and-strain-specific-effects-of-a-genotoxic-carcinogen-1-3-butadiene-on-chromatin-and-transcription
#14
Jennifer W Israel, Grace A Chappell, Jeremy M Simon, Sebastian Pott, Alexias Safi, Lauren Lewis, Paul Cotney, Hala S Boulos, Wanda Bodnar, Jason D Lieb, Gregory E Crawford, Terrence S Furey, Ivan Rusyn
Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control of transcription, and understanding of the chemical effects on both could inform the causal role of epigenetic alterations in disease mechanisms. In this study, we hypothesized that baseline variability in chromatin organization and transcription profiles among various tissues and mouse strains influence the outcome of exposure to the DNA damaging chemical 1,3-butadiene...
February 10, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29423272/loss-of-asxl1-in-the-bone-marrow-niche-dysregulates-hematopoietic-stem-and-progenitor-cell-fates
#15
Peng Zhang, Zizhen Chen, Rong Li, Ying Guo, Hui Shi, Jie Bai, Hui Yang, Mengyao Sheng, Zhaomin Li, Zhuo Li, Jianping Li, Shi Chen, Weiping Yuan, Tao Cheng, Mingjiang Xu, Yuan Zhou, Feng-Chun Yang
Somatic or de novo mutations of Additional sex combs-like 1 (ASXL1) frequently occur in patients with myeloid malignancies or Bohring-Opitz syndrome, respectively. We have reported that global loss of Asxl1 leads to the development of myeloid malignancies and impairs bone marrow stromal cell (BMSC) fates in mice. However, the impact of Asxl1 deletion in the BM niche on hematopoiesis remains unclear. Here, we showed that BMSCs derived from chronic myelomonocytic leukemia patients had reduced expression of ASXL1, which impaired the maintaining cord blood CD34+ cell colony-forming capacity with a myeloid differentiation bias...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29420797/octopus-toolkit-a-workflow-to-automate-mining-of-public-epigenomic-and-transcriptomic-next-generation-sequencing-data
#16
Taemook Kim, Hogyu David Seo, Lothar Hennighausen, Daeyoup Lee, Keunsoo Kang
Octopus-toolkit is a stand-alone application for retrieving and processing large sets of next-generation sequencing (NGS) data with a single step. Octopus-toolkit is an automated set-up-and-analysis pipeline utilizing the Aspera, SRA Toolkit, FastQC, Trimmomatic, HISAT2, STAR, Samtools, and HOMER applications. All the applications are installed on the user's computer when the program starts. Upon the installation, it can automatically retrieve original files of various epigenomic and transcriptomic data sets, including ChIP-seq, ATAC-seq, DNase-seq, MeDIP-seq, MNase-seq and RNA-seq, from the gene expression omnibus data repository...
February 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29416069/senataxin-resolves-rna-dna-hybrids-forming-at-dna-double-strand-breaks-to-prevent-translocations
#17
Sarah Cohen, Nadine Puget, Yea-Lih Lin, Thomas Clouaire, Marion Aguirrebengoa, Vincent Rocher, Philippe Pasero, Yvan Canitrot, Gaëlle Legube
Ataxia with oculomotor apraxia 2 (AOA-2) and amyotrophic lateral sclerosis (ALS4) are neurological disorders caused by mutations in the gene encoding for senataxin (SETX), a putative RNA:DNA helicase involved in transcription and in the maintenance of genome integrity. Here, using ChIP followed by high throughput sequencing (ChIP-seq), we report that senataxin is recruited at DNA double-strand breaks (DSBs) when they occur in transcriptionally active loci. Genome-wide mapping unveiled that RNA:DNA hybrids accumulate on DSB-flanking chromatin but display a narrow, DSB-induced, depletion near DNA ends coinciding with senataxin binding...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29413898/lrp6-is-a-target-of-the-pth-activated-%C3%AE-nac-transcriptional-coregulator
#18
Martin Pellicelli, Hadla Hariri, Julie A Miller, René St-Arnaud
In the nucleus of differentiated osteoblasts, the alpha chain of nascent polypeptide associated complex (αNAC) interacts with cJUN transcription factors to regulate the expression of target genes, including Osteocalcin (Bglap2). PTH induces the phosphorylation of αNAC on serine 99 through a Gαs-PKA dependent pathway. This leads to activation of αNAC and expression of Bglap2. To identify additional target genes regulated by PTH-activated αNAC, we performed ChIP-Seq against αNAC in PTH-treated MC3T3-E1 cells...
January 27, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29412141/integration-of-human-pancreatic-islet-genomic-data-refines-regulatory-mechanisms-at-type-2-diabetes-susceptibility-loci
#19
Matthias Thurner, Martijn van de Bunt, Jason M Torres, Anubha Mahajan, Vibe Nylander, Amanda J Bennett, Kyle J Gaulton, Amy Barrett, Carla Burrows, Christopher G Bell, Robert Lowe, Stephan Beck, Vardhman K Rakyan, Anna L Gloyn, Mark I McCarthy
Human genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development of Type 2 Diabetes (T2D). However, limited annotation of the islet epigenome has constrained efforts to define the molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns of chromatin accessibility (ATAC-seq, n=17) and DNA methylation (whole-genome bisulphite sequencing, n=10) in human islets, generating high-resolution chromatin state maps through integration with established ChIP-seq marks...
February 7, 2018: ELife
https://www.readbyqxmd.com/read/29396371/genome-wide-analysis-of-pdx1-target-genes-in-human-pancreatic-progenitors
#20
Xianming Wang, Michael Sterr, Ingo Burtscher, Shen Chen, Anja Hieronimus, Fausto Machicao, Harald Staiger, Hans-Ulrich Häring, Gabriele Lederer, Thomas Meitinger, Filippo M Cernilogar, Gunnar Schotta, Martin Irmler, Johannes Beckers, Martin Hrabě de Angelis, Michael Ray, Christopher V E Wright, Mostafa Bakhti, Heiko Lickert
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far...
January 30, 2018: Molecular Metabolism
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