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Celine Tasset, Avilash Singh Yadav, Sridevi Sureshkumar, Rupali Singh, Lennard van der Woude, Maxim Nekrasov, David Tremethick, Martijn van Zanten, Sureshkumar Balasubramanian
Ambient temperature affects plant growth and even minor changes can substantially impact crop yields. The underlying mechanisms of temperature perception and response are just beginning to emerge. Chromatin remodeling, via the eviction of the histone variant H2A.Z containing nucleosomes, is a critical component of thermal response in plants. However, the role of histone modifications remains unknown. Here, through a forward genetic screen, we identify POWERDRESS (PWR), a SANT-domain containing protein known to interact with HISTONE DEACETYLASE 9 (HDA9), as a novel factor required for thermomorphogenesis in Arabidopsis thaliana...
March 16, 2018: PLoS Genetics
Qian Li, Jiao Chen, Xiaoying Li, Bomiao Cui, Yaping Fan, Ning Geng, Qianming Chen, Ping Zhang, Yun Feng
High mobility group nucleosomal-binding domain 2 (HMGN2) is an abundant non-histone nuclear protein of vertebrates and invertebrates. The aim of the present study was to characterize the endogenous expression of HMGN2 in various types of tumor cell. Western blotting was performed to analyze HMGN2 expression in the following tumor cell lines: H1975, HSC-4, MDA-MB-468, MDA-MB-231, SCC-25 and THP-1. Periodontal ligament cells (PDLCs) were included as a noncancerous control. HMGN2 was detected in human oral squamous cell carcinoma tissues by immunohistochemical analysis...
April 2018: Oncology Letters
Sigrun Schmähling, Arno Meiler, Yoonjung Lee, Arif Mohammed, Katja Finkl, Katharina Tauscher, Lars Israel, Marc Borath, Julia Philippou-Massier, Helmut Blum, Bianca Habermann, Axel Imhof, Ji-Joon Song, Jürg Müller
The Drosophila Ash1 protein is a trithorax-group (trxG) regulator that antagonizes Polycomb repression at HOX genes. Ash1 di-methylates lysine 36 in histone H3 (H3K36me2) but how this activity is controlled and at which genes it functions is not well understood. We show that Ash1 protein purified from Drosophila exists in a complex with MRG15 and Caf1 that we named AMC. In Drosophila and human AMC, MRG15 binds a conserved FxLP motif near the Ash1 SET domain and stimulates H3K36 di-methylation on nucleosomes...
March 14, 2018: Development
Louise Rasmussen, Ib Jarle Christensen, Marielle Herzog, Jake Micallef, Hans Jørgen Nielsen
The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC)...
February 13, 2018: Oncotarget
Philippa Melamed, Majd Haj, Yahav Yosefzon, Sergei Rudnizky, Andrea Wijeweera, Lilach Pnueli, Ariel Kaplan
Gonadotropin-releasing hormone (GnRH) stimulates the expression of multiple genes in the pituitary gonadotropes, most notably to induce synthesis of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), but also to ensure the appropriate functioning of these cells at the center of the mammalian reproductive endocrine axis. Aside from the activation of gene-specific transcription factors, GnRH stimulates through its membrane-bound receptor, alterations in the chromatin that facilitate transcription of its target genes...
2018: Frontiers in Endocrinology
Laurie Galvan, Laetitia Francelle, Marie-Claude Gaillard, Lucie de Longprez, Maria-Angeles Carrillo-de Sauvage, Géraldine Liot, Karine Cambon, Lev Stimmer, Sophie Luccantoni, Julien Flament, Julien Valette, Michel de Chaldée, Gwenaelle Auregan, Martine Guillermier, Charlène Joséphine, Fanny Petit, Caroline Jan, Margot Jarrige, Noëlle Dufour, Gilles Bonvento, Sandrine Humbert, Frédéric Saudou, Philippe Hantraye, Karine Merienne, Alexis-Pierre Bemelmans, Anselme L Perrier, Nicole Déglon, Emmanuel Brouillet
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (doublecortin like kinase 3), which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington's disease. Recent data obtained in studies related to cancer suggest DCLK3 could have an anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington's disease may render striatal neurons more susceptible to mutant huntingtin (mHtt)...
March 9, 2018: Brain: a Journal of Neurology
Amy E Campbell, Sean C Shadle, Sujatha Jagannathan, Jong-Won Lim, Rebecca Resnick, Rabi Tawil, Silvère M van der Maarel, Stephen J Tapscott
The DUX4 transcription factor is encoded by a retrogene embedded in each unit of the D4Z4 macrosatellite repeat. DUX4 is normally expressed in the cleavage-stage embryo, whereas chromatin repression prevents DUX4 expression in most somatic tissues. Failure of this repression causes facioscapulohumeral muscular dystrophy (FSHD) due to mis-expression of DUX4 in skeletal muscle. In this study, we used CRISPR/Cas9 engineered chromatin immunoprecipitation (enChIP) locus-specific proteomics to characterize D4Z4-associated proteins...
March 13, 2018: ELife
Kyuha Choi, Xiaohui Zhao, Andrew J Tock, Christophe Lambing, Charles J Underwood, Thomas J Hardcastle, Heïdi Serra, Juhyun Kim, Hyun Seob Cho, Jaeil Kim, Piotr A Ziolkowski, Nataliya E Yelina, Ildoo Hwang, Robert A Martienssen, Ian R Henderson
Meiotic recombination initiates from DNA double-strand breaks (DSBs) generated by SPO11 topoisomerase-like complexes. Meiotic DSB frequency varies extensively along eukaryotic chromosomes, with hotspots controlled by chromatin and DNA sequence. To map meiotic DSBs throughout a plant genome, we purified and sequenced Arabidopsis thaliana SPO11-1-oligonucleotides. SPO11-1-oligos are elevated in gene promoters, terminators, and introns, which is driven by AT-sequence richness that excludes nucleosomes and allows SPO11-1 access...
March 12, 2018: Genome Research
Hyewon Shin, Minzhen He, Zhi Yang, Yong Heui Jeon, Jessica Pfleger, Danish Sayed, Maha Abdellatif
The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.Z in a yeast two-hybrid screen. Knockdown of ANP32e resulted in proteasomal degradation and nuclear depletion of H2A.Z or of a chimeric green florescence protein fused to its N-terminus. This effect was reversed by inhibition of protein phosphatase 2A (PP2A) and, conversely, reproduced by overexpression of its catalytic subunit...
March 7, 2018: Biochimica et Biophysica Acta
Vikas H Malojirao, V Vigneshwaran, Prabhu Thirusangu, Riaz Mahmood, B T Prabhakar
Aim Deformity in the cellular homeostatic event associated with cell survival and apoptosis are committing factors for carcinogenesis. Interventions of these events by pharmacologically active agent gain predominance in cancer treatment. In current investigation Solanidine, a steroidal alkaloid was evaluated on tumorigenesis by targeting death signal using multiple tumor cells and model systems. MAIN METHODS: Anti-proliferative effect was evaluated using cytotoxic studies. Prolonged cytotoxic effect of Solanidine was examined by colony formation assay...
March 7, 2018: Life Sciences
Yun Jia, Hong Li, Jingfeng Wang, Hu Meng, Zhenhua Yang
The spectra of k-mer frequencies can reveal the structures and evolution of genome sequences. We confirmed that the trimodal spectrum of 8-mers in human genome sequences is distinguished only by CG2, CG1 and CG0 8-mer sets respectively. This phenomenon is called independent selection law. The three types of CG 8-mers were considered as different functional elements. We conjectured that (1) nucleosome binding motifs are mainly characterized by CG1 8-mers and (2) the core structural units of CpG island sequences are predominantly characterized by CG2 8-mers...
March 6, 2018: Genomics
Geetha S Hewawasam, Karthik Dhatchinamoorthy, Mark Mattingly, Chris Seidel, Jennifer L Gerton
Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast...
March 7, 2018: Nucleic Acids Research
Martyna Tomczyk-Socha, Hanna Sikorska-Szaflik, Marek Frankowski, Karolina Andrzejewska, Agnieszka Odziomek, Magdalena Szmyrka
BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with varied clinical manifestations, which creates difficulties and delays in establishing a diagnosis. OBJECTIVES: The aim of this study was to evaluate the prevalence and nature of the clinical symptoms of SLE, both at the onset of the disease and in its further course. An attempt to assess the immunological characteristics of the patients and to analyze autoantibodies variability over time was also made...
January 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
K H Lee, L Cavanaugh, H Leung, F Yan, Z Ahmadi, B H Chong, F Passam
INTRODUCTION: Neutrophil extracellular traps (NETs) are networks of extracellular fibres produced from neutrophil DNA with a pathogenic role in infection, thrombosis and other conditions. Reliable assays for measuring NETs are desirable as novel treatments targeting NETs are being explored for the treatment of these conditions. We compare a whole blood flow cytometry method with serum assays to measure NETs-associated markers in patients with sepsis and thrombosis. METHODS: Patients with deep venous thrombosis (n = 25), sepsis (n = 21) and healthy controls (n = 23) were included in the study...
March 9, 2018: International Journal of Laboratory Hematology
Fahim Ebrahimi, Stavros Giaglis, Sinuhe Hahn, Claudine A Blum, Christine Baumgartner, Alexander Kutz, Shane Vontelin van Breda, Beat Mueller, Philipp Schuetz, Mirjam Christ-Crain, Paul Hasler
Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomized-controlled, multicentre trial. Patients with community-acquired pneumonia were randomly assigned to either prednisone 50 mg or placebo for 7 days. The primary endpoint was time to clinical stability; main secondary endpoints were length of hospital stay and mortality...
March 8, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Francesca Mattiroli, Yajie Gu, Karolin Luger
Nucleosomes organize the eukaryotic genome into chromatin. In cells, nucleosome assembly relies on the activity of histone chaperones, proteins with high binding affinity to histones. At least a subset of histone chaperones promotes histone deposition in vivo . However, it has been challenging to characterize this activity, due to the lack of quantitative assays. Here we developed a quantitative nucleosome assembly (NAQ) assay to measure the amount of nucleosome formation in vitro . This assay relies on a Micrococcal nuclease (MNase) digestion step that yields DNA fragments protected by the deposited histone proteins...
February 5, 2018: Bio-protocol
Jean Davidson, Zhewei Shen, Xue Gong, Jonathan R Pollack
While gemcitabine has been the mainstay therapy for advanced pancreatic cancer, newer combination regimens (e.g. FOLFIRINOX) have extended patient survival, though carry greater toxicity. Biomarkers are needed to better stratify patients for appropriate therapy. Previously, we reported that one-third of pancreatic cancers harbor deletions or deleterious mutations in key subunits of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. The SWI/SNF complex mobilizes nucleosomes on DNA, and plays a key role in modulating DNA transcription and repair...
February 9, 2018: Oncotarget
Hironori Funabiki, Christopher Jenness, Christian Zierhut
The majority of eukaryotic chromosomal DNA exists in the form of nucleosomes, where ∼147 bp DNA wraps around histone hetero-octamers, composed of histone H3, H4, H2A, and H2B. Despite their obvious importance in DNA compaction and accessibility, studying their specific roles, such as regulation of mitotic progression, in a physiological environment is associated with critical caveats because of their major contributions in transcriptional control. Through establishing a method to deplete endogenous histones H3 and H4 from frog egg extracts and complementing their functions using recombinant nucleosome arrays, we are now able to analyze their roles in mitotic progression without affecting overall transcriptomic profiles...
March 7, 2018: Cold Spring Harbor Symposia on Quantitative Biology
Laura L McCullough, Zaily Connell, Hua Xin, Vasily M Studitsky, Alexey V Feofanov, Maria E Valieva, Tim Formosa
The essential histone chaperone FAcilitates Chromatin Transcription (FACT) promotes both nucleosome assembly and disassembly. FACT is a heterodimer of Spt16 with either SSRP1 or Pob3, differing primarily by the presence of a high-mobility group B (HMGB) DNA-binding domain furnished only by SSRP1. Yeast FACT lacks the intrinsic HMGB domain found in SSRP1-based homologs such as human FACT, but yeast FACT activity is supported by Nhp6, which is a freestanding, single HMGB domain protein. The importance of histone binding by FACT domains has been established, but the roles of DNA binding activity remain poorly understood...
March 7, 2018: Journal of Biological Chemistry
Savrina Manhas, Lina Ma, Vivien Measday
Nuclear pore complexes (NPCs) orchestrate cargo between the cytoplasm and nucleus and regulate chromatin organization. NPC proteins, or nucleoporins (Nups), are required for human immunodeficiency virus type 1 (HIV-1) gene expression and genomic integration of viral DNA. We utilize the Ty1 retrotransposon of Saccharomyces cerevisiae (S. cerevisiae) to study retroviral integration because retrotransposons are the progenitors of retroviruses and have conserved integrase (IN) enzymes. Ty1-IN targets Ty1 elements into the genome upstream of RNA polymerase (Pol) III transcribed genes such as transfer RNA (tRNA) genes...
March 5, 2018: Nucleic Acids Research
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