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Chromatin-associated RNA

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https://www.readbyqxmd.com/read/28223370/the-lim-only-protein-fhl2-is-a-negative-regulator-of-tgf-%C3%AE-1-expression
#1
Jennifer Dahan, Florence Levillayer, Tian Xia, Yann Nouët, Catherine Werts, Martine Fanton d'Andon, Minou Adib-Conquy, Anne-Marie Cassard-Doulcier, Varun Khanna, Ju Chen, Thierry Tordjmann, Marie-Annick Buendia, Grégory Jouvion, Yu Wei
TGF-β1 is a master cytokine in many biological processes including tissue homeostasis, epithelial to mesenchymal transition and wound repair. Here we report that the four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of DNA-binding domain, FHL2 is a transcriptional co-factor that plays the role of co-activator or co-repressor depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2(-/-) cells than WT cells in a reporter assay...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28219892/an-infectious-disease-associated-il12b-polymorphism-regulates-il-12-23-p40-transcription-involving-poly-adp-ribose-polymerase-1
#2
Quanju Zhao, Qinglin Du, Fang Wei, Jianping Xie, Xiaojing Ma
IL-12 and IL-23 are important host defense factors produced by APCs against certain intracellular and extracellular pathogens. Their dysregulation has also been implicated in several autoimmune diseases. The nucleotide polymorphism in the promoter region of Il12b (rs41292470 consisting of the long or short allele) encoding the shared subunit of IL-12 and IL-23, p40, has been reported to associate with susceptibility to infectious diseases and autoimmune disorders. How these genetic variants impact Il12b expression at the molecular level was unclear...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219335/stress-responsive-pathways-and-small-rna-changes-distinguish-variable-developmental-phenotypes-caused-by-msh1-loss
#3
Mon-Ray Shao, Sunil Kumar Kenchanmane Raju, John D Laurie, Robersy Sanchez, Sally A Mackenzie
BACKGROUND: Proper regulation of nuclear-encoded, organelle-targeted genes is crucial for plastid and mitochondrial function. Among these genes, MutS Homolog 1 (MSH1) is notable for generating an assortment of mutant phenotypes with varying degrees of penetrance and pleiotropy. Stronger phenotypes have been connected to stress tolerance and epigenetic changes, and in Arabidopsis T-DNA mutants, two generations of homozygosity with the msh1 insertion are required before severe phenotypes begin to emerge...
February 20, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28218250/chromatin-remodeller-fun30-fft3-induces-nucleosome-disassembly-to-facilitate-rna-polymerase-ii-elongation
#4
Junwoo Lee, Eun Shik Choi, Hogyu David Seo, Keunsoo Kang, Joshua M Gilmore, Laurence Florens, Michael P Washburn, Joonho Choe, Jerry L Workman, Daeyoup Lee
Previous studies have revealed that nucleosomes impede elongation of RNA polymerase II (RNAPII). Recent observations suggest a role for ATP-dependent chromatin remodellers in modulating this process, but direct in vivo evidence for this is unknown. Here using fission yeast, we identify Fun30(Fft3) as a chromatin remodeller, which localizes at transcribing regions to promote RNAPII transcription. Fun30(Fft3) associates with RNAPII and collaborates with the histone chaperone, FACT, which facilitates RNAPII elongation through chromatin, to induce nucleosome disassembly at transcribing regions during RNAPII transcription...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28217257/regulation-of-hepatic-microrna-expression-by-hepatocyte-nuclear-factor-4-alpha
#5
Hong Lu, Xiaohong Lei, Jerry Liu, Curtis Klaassen
AIM: To uncover the role of hepatocyte nuclear factor 4 alpha (HNF4α) in regulating hepatic expression of microRNAs. METHODS: Microarray and real-time PCR were used to determine hepatic expression of microRNAs in young-adult mice lacking Hnf4α expression in liver (Hnf4α-LivKO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-II, and histone modifications to loci of microRNAs in mouse liver and human hepatoma cells...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#6
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#7
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28209301/iswi-atp-dependent-remodeling-of-nucleoplasmic-%C3%AF-speckles-in-the-brain-of-drosophila-melanogaster
#8
Luca Lo Piccolo, Andrea Attardi, Rosa Bonaccorso, Lorenzo Li Greci, Giorgio Giurato, Antonia Maria Rita Ingrassia, Maria Cristina Onorati
Heterogeneous nuclear ribonucleoproteins (hnRNPs) belong to the RNA-binding proteins family. They are involved in processing heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs. These proteins participate in every step of mRNA cycle, such as mRNA export, localization, translation, stability and alternative splicing. At least 14 major hnRNPs, which have structural and functional homologues in mammals, are expressed in Drosophila melanogaster. Until now, six of these hnRNPs are known to be nucleus-localized and associated with the long non-coding RNA (lncRNA) heat shock responsive ω (hsrω) in the omega speckle compartments (ω-speckles)...
December 22, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#9
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28196804/nipped-a-regulates-intestinal-stem-cell-proliferation-in-drosophila
#10
Helen Marie Tauc, Alpaslan Tasdogan, Patrick Meyer, Petra Pandur
Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28193769/long-noncoding-rnas-at-the-intersection-of-cancer-and-chromatin-biology
#11
Adam M Schmitt, Howard Y Chang
Although only 2% of the genome encodes protein, RNA is transcribed from the majority of the genetic sequence, suggesting a massive degree of cellular functionality is programmed in the noncoding genome. The mammalian genome contains tens of thousands of long noncoding RNAs (lncRNAs), many of which occur at disease-associated loci or are specifically expressed in cancer. Although the vast majority of lncRNAs have no known function, recurring molecular mechanisms for lncRNAs are now being observed in chromatin regulation and cancer pathways and emerging technologies are now providing tools to interrogate lncRNA molecular interactions and determine function of these abundant cellular macromolecules...
February 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28190769/paf1-has-distinct-roles-in-transcription-elongation-and-differential-transcript-fate
#12
Harry Fischl, Françoise S Howe, Andre Furger, Jane Mellor
RNA polymerase II (Pol2) movement through chromatin and the co-transcriptional processing and fate of nascent transcripts is coordinated by transcription elongation factors (TEFs) such as polymerase-associated factor 1 (Paf1), but it is not known whether TEFs have gene-specific functions. Using strand-specific nucleotide resolution techniques, we show that levels of Paf1 on Pol2 vary between genes, are controlled dynamically by environmental factors via promoters, and reflect levels of processing and export factors on the encoded transcript...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28188267/phosphorylation-of-spt5-by-cdkd-2-is-required-for-vip5-recruitment-and-normal-flowering-in-arabidopsis-thaliana
#13
Chengyuan Lu, Yongke Tian, Shiliang Wang, Yanhua Su, Ting Mao, Tongtong Huang, Qingqing Chen, Zuntao Xu, Yong Ding
The elongation factor suppressor of Ty 5 homolog (Spt5) is a regulator of transcription and histone methylation. In humans, phosphorylation of SPT5 by P-TEFb, a protein kinase composed of Cyclin-dependent kinase 9 (CDK9) and cyclin T, interacts with the RNA polymerase II-associated factor1 (PAF1) complex. However, the mechanism of SPT5 phosphorylation is not well understood in plants. Here, we examine the function of SPT5 in Arabidopsis thaliana, and find that spt5 mutant flowers early under long-day and short-day conditions...
February 10, 2017: Plant Cell
https://www.readbyqxmd.com/read/28185826/chaetocin-a-histone-methyltransferase-inhibitor-impairs-proliferation-arrests-cell-cycle-and-induces-nucleolar-disassembly-in-trypanosoma-cruzi
#14
Aline Araujo Zuma, Jean de Oliveira Santos, Isabela Mendes, Wanderley de Souza, Carlos Renato Machado, E Maria Cristina M Motta
The Trypanosomatidae family includes pathogenic species of medical and veterinary interest. Chagas disease is endemic in Latin America, and about 8 million people are infected worldwide. There is a need for more effective drugs for the acute, undetermined and chronic phases of the disease that, in addition, do not cause side effects, stimulating the search for identification of new drug targets, as well as new chemotherapeutic targets. Trypanosomatids contain characteristic structures, such as the nucleus that undergoes a closed mitosis without chromosome formation and variations of chromatin packing in the different protozoa developmental stages...
February 6, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28178938/messenger-rna-and-microrna-transcriptomic-signatures-of-cardiometabolic-risk-factors
#15
David D McManus, Jian Rong, Tianxiao Huan, Sean Lacey, Kahraman Tanriverdi, Peter J Munson, Martin G Larson, Roby Joehanes, Venkatesh Murthy, Ravi Shah, Jane E Freedman, Daniel Levy
BACKGROUND: Cardiometabolic (CM) risk factors are heritable and cluster in individuals. We hypothesized that CM risk factors are associated with multiple shared and unique mRNA and microRNA (miRNA) signatures. We examined associations of mRNA and miRNA levels with 6 CM traits: body mass index, HDL-cholesterol and triglycerides, fasting glucose, and systolic and diastolic blood pressures through cross-sectional analysis of 2812 Framingham Heart Study who had whole blood collection for RNA isolation for mRNA and miRNA expression studies and who consented to genetic research...
February 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28177766/functional-assessment-of-mecp2-in-rett-syndrome-and-cancers-of-breast-colon-and-prostate
#16
Somnath Pandey, Kevin Pruitt
Ever since the first report that mutations in methyl-CpG-binding protein 2 (MeCP2) causes Rett syndrome (RTT), a severe neurological disorder in females world-wide, there has been a keen interest to gain a comprehensive understanding of this protein. While the classical model associated with MeCP2 function suggests its role in gene suppression via recruitment of co-repressor complexes and histone deacetylases to methylated CpG-sites, recent discoveries have brought to light its role in transcription activation, modulation of RNA splicing and chromatin compaction...
November 10, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28176797/nucleosome-positioning-and-ndr-structure-at-rna-polymerase-iii-promoters
#17
Alexandra Søgaard Helbo, Fides D Lay, Peter A Jones, Gangning Liang, Kirsten Grønbæk
Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high-resolution analysis to show substantial differences in chromatin structure of pol II and pol III promoters, and between subtypes of pol III genes. Notably, the nucleosome depleted region at the transcription start site of pol III genes extends past the termination sequences, resulting in nucleosome free gene bodies...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167501/comprehensive-characterization-of-neutrophil-genome-topology
#18
Yina Zhu, Ke Gong, Matthew Denholtz, Vivek Chandra, Mark P Kamps, Frank Alber, Cornelis Murre
Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei are uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found that neutrophil differentiation was not associated with large-scale changes in the number and sizes of topologically associating domains (TADs). However, neutrophil genomes were enriched for long-range genomic interactions that spanned multiple TADs. Population-based simulation of spherical and toroid genomes revealed declining radii of gyration for neutrophil chromosomes...
February 6, 2017: Genes & Development
https://www.readbyqxmd.com/read/28166799/toll-like-receptor-3-activation-selectively-reverses-hiv-latency-in-microglial-cells
#19
David Alvarez-Carbonell, Yoelvis Garcia-Mesa, Stephanie Milne, Biswajit Das, Curtis Dobrowolski, Roxana Rojas, Jonathan Karn
BACKGROUND: Multiple toll-like receptors (TLRs) are expressed in cells of the monocytic lineage, including microglia, which constitute the major reservoir for human immunodeficiency virus (HIV) infection in the brain. We hypothesized that TLR receptor mediated responses to inflammatory conditions by microglial cells in the central nervous system (CNS) are able to induce latent HIV proviruses, and contribute to the etiology of HIV-associated neurocognitive disorders. RESULTS: Newly developed human microglial cell lines (hµglia), obtained by immortalizing human primary microglia with simian virus-40 (SV40) large T antigen and the human telomerase reverse transcriptase, were used to generate latently infected cells using a single-round HIV virus carrying a green fluorescence protein reporter (hµglia/HIV, clones HC01 and HC69)...
February 6, 2017: Retrovirology
https://www.readbyqxmd.com/read/28159836/c-myc-downregulation-is-required-for-preacinar-to-acinar-maturation-and-pancreatic-homeostasis
#20
Victor J Sánchez-Arévalo Lobo, Luis César Fernández, Enrique Carrillo-de-Santa-Pau, Laia Richart, Isidoro Cobo, Jaroslaw Cendrowski, Ulisses Moreno, Natalia Del Pozo, Diego Megías, Bernardette Bréant, Christopher V Wright, Mark Magnuson, Francisco X Real
BACKGROUND AND AIMS: c-Myc is highly expressed in pancreatic multipotent progenitor cells (MPC) and in pancreatic cancer. The transition from MPC to unipotent acinar progenitors is associated with c-Myc downregulation; a role for c-Myc in this process, and its possible relationship to a role in cancer, has not been established. DESIGN: Using coimmunoprecipitation assays, we demonstrate that c-Myc and Ptf1a interact. Using reverse transcriptase qPCR, western blot and immunofluorescence, we show the erosion of the acinar programme...
February 3, 2017: Gut
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