Dynamics of Gene Silencing During X Inactivation Using Allele-Specific RNA-Seq Hendrik Marks1*, Hindrik H
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Open Dogan Phdthesis Final.Pdf
The Pennsylvania State University The Graduate School Eberly College of Science ELUCIDATING BIOLOGICAL FUNCTION OF GENOMIC DNA WITH ROBUST SIGNALS OF BIOCHEMICAL ACTIVITY: INTEGRATIVE GENOME-WIDE STUDIES OF ENHANCERS A Dissertation in Biochemistry, Microbiology and Molecular Biology by Nergiz Dogan © 2014 Nergiz Dogan Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2014 ii The dissertation of Nergiz Dogan was reviewed and approved* by the following: Ross C. Hardison T. Ming Chu Professor of Biochemistry and Molecular Biology Dissertation Advisor Chair of Committee David S. Gilmour Professor of Molecular and Cell Biology Anton Nekrutenko Professor of Biochemistry and Molecular Biology Robert F. Paulson Professor of Veterinary and Biomedical Sciences Philip Reno Assistant Professor of Antropology Scott B. Selleck Professor and Head of the Department of Biochemistry and Molecular Biology *Signatures are on file in the Graduate School iii ABSTRACT Genome-wide measurements of epigenetic features such as histone modifications, occupancy by transcription factors and coactivators provide the opportunity to understand more globally how genes are regulated. While much effort is being put into integrating the marks from various combinations of features, the contribution of each feature to accuracy of enhancer prediction is not known. We began with predictions of 4,915 candidate erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues. -
Lncrna Jpx Induces Xist Expression in Mice Using Both Trans and Cis Mechanisms
RESEARCH ARTICLE LncRNA Jpx induces Xist expression in mice using both trans and cis mechanisms Sarah Carmona, Benjamin Lin, Tristan Chou, Katti Arroyo, Sha Sun* Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, Irvine, CA, United States of America * [email protected] a1111111111 a1111111111 Abstract a1111111111 a1111111111 Mammalian X chromosome dosage compensation balances X-linked gene products a1111111111 between sexes and is coordinated by the long noncoding RNA (lncRNA) Xist. Multiple cis and trans-acting factors modulate Xist expression; however, the primary competence factor responsible for activating Xist remains a subject of dispute. The lncRNA Jpx is a proposed competence factor, yet it remains unknown if Jpx is sufficient to activate Xist expression in OPEN ACCESS mice. Here, we utilize a novel transgenic mouse system to demonstrate a dose-dependent relationship between Jpx copy number and ensuing Jpx and Xist expression. By localizing Citation: Carmona S, Lin B, Chou T, Arroyo K, Sun S (2018) LncRNA Jpx induces Xist expression in transcripts of Jpx and Xist using RNA Fluorescence in situ Hybridization (FISH) in mouse mice using both trans and cis mechanisms. PLoS embryonic cells, we provide evidence of Jpx acting in both trans and cis to activate Xist. Our Genet 14(5): e1007378. https://doi.org/10.1371/ data contribute functional and mechanistic insight for lncRNA activity in mice, and argue that journal.pgen.1007378 Jpx is a competence factor for Xist activation in vivo. Editor: Gregory S. Barsh, Stanford University School of Medicine, UNITED STATES Received: November 20, 2017 Accepted: April 24, 2018 Author summary Published: May 7, 2018 Long noncoding RNA (lncRNA) have been identified in all eukaryotes but mechanisms Copyright: © 2018 Carmona et al. -
Repetitive Elements in Humans
International Journal of Molecular Sciences Review Repetitive Elements in Humans Thomas Liehr Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, D-07747 Jena, Germany; [email protected] Abstract: Repetitive DNA in humans is still widely considered to be meaningless, and variations within this part of the genome are generally considered to be harmless to the carrier. In contrast, for euchromatic variation, one becomes more careful in classifying inter-individual differences as meaningless and rather tends to see them as possible influencers of the so-called ‘genetic background’, being able to at least potentially influence disease susceptibilities. Here, the known ‘bad boys’ among repetitive DNAs are reviewed. Variable numbers of tandem repeats (VNTRs = micro- and minisatellites), small-scale repetitive elements (SSREs) and even chromosomal heteromorphisms (CHs) may therefore have direct or indirect influences on human diseases and susceptibilities. Summarizing this specific aspect here for the first time should contribute to stimulating more research on human repetitive DNA. It should also become clear that these kinds of studies must be done at all available levels of resolution, i.e., from the base pair to chromosomal level and, importantly, the epigenetic level, as well. Keywords: variable numbers of tandem repeats (VNTRs); microsatellites; minisatellites; small-scale repetitive elements (SSREs); chromosomal heteromorphisms (CHs); higher-order repeat (HOR); retroviral DNA 1. Introduction Citation: Liehr, T. Repetitive In humans, like in other higher species, the genome of one individual never looks 100% Elements in Humans. Int. J. Mol. Sci. alike to another one [1], even among those of the same gender or between monozygotic 2021, 22, 2072. -
SLIC-CAGE: High-Resolution Transcription Start Site Mapping Using Nanogram-Levels of Total RNA
bioRxiv preprint doi: https://doi.org/10.1101/368795; this version posted July 19, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA Nevena Cvetesic1, 2*, Harry G. Leitch1,2, Malgorzata Borkowska1,2, Ferenc Müller3, Piero Carninci4,5, Petra Hajkova1,2 and Boris Lenhard1,2,6* 1Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK 2MRC London Institute of Medical Sciences, London W12 0NN, UK 3Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston B15 2TT, UK 4RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama City, Kanagawa 230-0045, Japan 5RIKEN Omics Science Center, Yokohama City, Kanagawa 230-0045, Japan 6Sars International Centre for Marine Molecular Biology, University of Bergen, N-5008 Bergen, Norway *Correspondence to: Nevena Cvetesic Institute of Clinical Sciences, Faculty of Medicine, Imperial College London and MRC London Institute of Medical Sciences, London, W12 0NN, UK e-mail: [email protected] Boris Lenhard Institute of Clinical Sciences, Faculty of Medicine, Imperial College London and MRC London Institute of Medical Sciences, London, W12 0NN, UK e-mail: [email protected] Running title: TSS discovery using Super-Low Input Carrier-CAGE Keywords: cap analysis of gene expression; low input material; degradable nucleic acid carrier; promoters; gene expression profiling 1 bioRxiv preprint doi: https://doi.org/10.1101/368795; this version posted July 19, 2018. -
The Role of Non-Coding Rnas in Uveal Melanoma
cancers Review The Role of Non-Coding RNAs in Uveal Melanoma Manuel Bande 1,2,*, Daniel Fernandez-Diaz 1,2, Beatriz Fernandez-Marta 1, Cristina Rodriguez-Vidal 3, Nerea Lago-Baameiro 4, Paula Silva-Rodríguez 2,5, Laura Paniagua 6, María José Blanco-Teijeiro 1,2, María Pardo 2,4 and Antonio Piñeiro 1,2 1 Department of Ophthalmology, University Hospital of Santiago de Compostela, Ramon Baltar S/N, 15706 Santiago de Compostela, Spain; [email protected] (D.F.-D.); [email protected] (B.F.-M.); [email protected] (M.J.B.-T.); [email protected] (A.P.) 2 Tumores Intraoculares en el Adulto, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain; [email protected] (P.S.-R.); [email protected] (M.P.) 3 Department of Ophthalmology, University Hospital of Cruces, Cruces Plaza, S/N, 48903 Barakaldo, Vizcaya, Spain; [email protected] 4 Grupo Obesidómica, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain; [email protected] 5 Fundación Pública Galega de Medicina Xenómica, Clinical University Hospital, SERGAS, 15706 Santiago de Compostela, Spain 6 Department of Ophthalmology, University Hospital of Coruña, Praza Parrote, S/N, 15006 La Coruña, Spain; [email protected] * Correspondence: [email protected]; Tel.: +34-981951756; Fax: +34-981956189 Received: 13 September 2020; Accepted: 9 October 2020; Published: 12 October 2020 Simple Summary: The development of uveal melanoma is a multifactorial and multi-step process, in which abnormal gene expression plays a key role. -
XIST Induced by JPX Suppresses Hepatocellular Carcinoma by Sponging Mir-155-5P
Original Article Yonsei Med J 2018 Sep;59(7):816-826 https://doi.org/10.3349/ymj.2018.59.7.816 pISSN: 0513-5796 · eISSN: 1976-2437 XIST Induced by JPX Suppresses Hepatocellular Carcinoma by Sponging miR-155-5p Xiu-qing Lin, Zhi-ming Huang, Xin Chen, Fang Wu, and Wei Wu Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Purpose: The influence of X-inactive specific transcript (XIST) and X-chromosome inactivation associated long non-coding RNAs (lncRNAs) just proximal to XIST (JPX) on hepatocellular carcinoma (HCC) remains controversial in light of previous reports, which the present study aimed to verify. Materials and Methods: The DIANA lncRNA-microRNA (miRNA) interaction database was used to explore miRNA interactions with JPX or XIST. JPX, XIST, and miR-155-5p expression levels in paired HCC specimens and adjacent normal tissue were ana- lyzed by RT-qPCR. Interaction between XIST and miR-155-5p was verified by dual luciferase reporter assay. Expression levels of miR-155-5p and its known target genes, SOX6 and PTEN, were verified by RT-qPCR and Western blot in HepG2 cells with or with- out XIST knock-in. The potential suppressive role of XIST and JPX on HCC was verified by cell functional assays and tumor for- mation assay using a xenograft model. Results: JPX and XIST expression was significantly decreased in HCC pathologic specimens, compared to adjacent tissue, which correlated with HCC progression and increased miR-155-5p expression. Dual luciferase reporter assay revealed XIST as a direct target of miR-155-5p. -
Drosophila and Human Transcriptomic Data Mining Provides Evidence for Therapeutic
Drosophila and human transcriptomic data mining provides evidence for therapeutic mechanism of pentylenetetrazole in Down syndrome Author Abhay Sharma Institute of Genomics and Integrative Biology Council of Scientific and Industrial Research Delhi University Campus, Mall Road Delhi 110007, India Tel: +91-11-27666156, Fax: +91-11-27662407 Email: [email protected] Nature Precedings : hdl:10101/npre.2010.4330.1 Posted 5 Apr 2010 Running head: Pentylenetetrazole mechanism in Down syndrome 1 Abstract Pentylenetetrazole (PTZ) has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS). The mechanism underlying PTZ’s therapeutic effect is however not clear. Microarray profiling has previously reported differential expression of genes in DS. No mammalian transcriptomic data on PTZ treatment however exists. Nevertheless, a Drosophila model inspired by rodent models of PTZ induced kindling plasticity has recently been described. Microarray profiling has shown PTZ’s downregulatory effect on gene expression in fly heads. In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential mechanism of PTZ action in DS. I find that transcriptomic correlates of chronic PTZ in Drosophila and DS counteract each other. A significant enrichment is observed between PTZ downregulated and DS upregulated genes, and a significant depletion between PTZ downregulated and DS dowwnregulated genes. Further, the common genes in PTZ Nature Precedings : hdl:10101/npre.2010.4330.1 Posted 5 Apr 2010 downregulated and DS upregulated sets show enrichment for MAP kinase pathway. My analysis suggests that downregulation of MAP kinase pathway may mediate therapeutic effect of PTZ in DS. Existing evidence implicating MAP kinase pathway in DS supports this observation. -
Product Data Sheet
For research purposes only, not for human use Product Data Sheet GRIPAP1 siRNA (Mouse) Catalog # Source Reactivity Applications CRM5563 Synthetic M RNAi Description siRNA to inhibit GRIPAP1 expression using RNA interference Specificity GRIPAP1 siRNA (Mouse) is a target-specific 19-23 nt siRNA oligo duplexes designed to knock down gene expression. Form Lyophilized powder Gene Symbol GRIPAP1 Alternative Names DXIMX47E; KIAA1167; GRIP1-associated protein 1; GRASP-1; HCMV-interacting protein Entrez Gene 54645 (Mouse) SwissProt Q8VD04 (Mouse) Purity > 97% Quality Control Oligonucleotide synthesis is monitored base by base through trityl analysis to ensure appropriate coupling efficiency. The oligo is subsequently purified by affinity-solid phase extraction. The annealed RNA duplex is further analyzed by mass spectrometry to verify the exact composition of the duplex. Each lot is compared to the previous lot by mass spectrometry to ensure maximum lot-to-lot consistency. Components We offers pre-designed sets of 3 different target-specific siRNA oligo duplexes of mouse GRIPAP1 gene. Each vial contains 5 nmol of lyophilized siRNA. The duplexes can be transfected individually or pooled together to achieve knockdown of the target gene, which is most commonly assessed by qPCR or western blot. Our siRNA oligos are also chemically modified (2’-OMe) at no extra charge for increased stability and enhanced knockdown in vitro and in vivo. Application key: E- ELISA, WB- Western blot, IH- Immunohistochemistry, IF- Immunofluorescence, FC- Flow cytometry, -
Limma: Linear Models for Microarray and RNA-Seq Data User’S Guide
limma: Linear Models for Microarray and RNA-Seq Data User's Guide Gordon K. Smyth, Matthew Ritchie, Natalie Thorne, James Wettenhall, Wei Shi and Yifang Hu Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia First edition 2 December 2002 Last revised 14 July 2021 This free open-source software implements academic research by the authors and co-workers. If you use it, please support the project by citing the appropriate journal articles listed in Section 2.1. Contents 1 Introduction 5 2 Preliminaries 7 2.1 Citing limma ......................................... 7 2.2 Installation . 9 2.3 How to get help . 9 3 Quick Start 11 3.1 A brief introduction to R . 11 3.2 Sample limma Session . 12 3.3 Data Objects . 13 4 Reading Microarray Data 15 4.1 Scope of this Chapter . 15 4.2 Recommended Files . 15 4.3 The Targets Frame . 15 4.4 Reading Two-Color Intensity Data . 17 4.5 Reading Single-Channel Agilent Intensity Data . 19 4.6 Reading Illumina BeadChip Data . 19 4.7 Image-derived Spot Quality Weights . 20 4.8 Reading Probe Annotation . 21 4.9 Printer Layout . 22 4.10 The Spot Types File . 22 5 Quality Assessment 24 6 Pre-Processing Two-Color Data 26 6.1 Background Correction . 26 6.2 Within-Array Normalization . 28 6.3 Between-Array Normalization . 30 6.4 Using Objects from the marray Package . 33 7 Filtering unexpressed probes 34 1 8 Linear Models Overview 36 8.1 Introduction . 36 8.2 Single-Channel Designs . 37 8.3 Common Reference Designs . -
HHS Public Access Author Manuscript
HHS Public Access Author manuscript Author Manuscript Author ManuscriptCell. Author Author Manuscript manuscript; Author Manuscript available in PMC 2015 November 06. Published in final edited form as: Cell. 2014 November 6; 159(4): 869–883. doi:10.1016/j.cell.2014.10.019. ATRX Directs Binding of PRC2 to Xist RNA and Polycomb Targets Kavitha Sarma1,2,3, Catherine Cifuentes-Rojas1,2,3, Ayla Ergun2,3, Amanda del Rosario5, Yesu Jeon1,2,3, Forest White5, Ruslan Sadreyev2,3,4, and Jeannie T. Lee1,2,3,4,* 1Howard Hughes Medical Institute 2Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA 3Department of Genetics, Harvard Medical School, Boston, MA USA 4Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA 5Department of Bioengineering, Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA USA SUMMARY X chromosome inactivation (XCI) depends on the long noncoding RNA Xist and its recruitment of Polycomb Repressive Complex 2 (PRC2). PRC2 is also targeted to other sites throughout the genome to effect transcriptional repression. Using XCI as a model, we apply an unbiased proteomics approach to isolate Xist and PRC2 regulators and identified ATRX. ATRX unexpectedly functions as a high-affinity RNA-binding protein that directly interacts with RepA/ Xist RNA to promote loading of PRC2 in vivo. Without ATRX, PRC2 cannot load onto Xist RNA nor spread in cis along the X chromosome. Moreover, epigenomic profiling reveals that genome- wide targeting of PRC2 depends on ATRX, as loss of ATRX leads to spatial redistribution of PRC2 and derepression of Polycomb responsive genes. -
Integrative Analysis of Multiple Sclerosis Using a Systems Biology
www.nature.com/scientificreports OPEN Integrative analysis of Multiple Sclerosis using a systems biology approach Received: 21 July 2017 Karla Cervantes-Gracia1 & Holger Husi 2,3 Accepted: 23 March 2018 Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by infammatory-demyelinating Published: xx xx xxxx events in the central nervous system. Despite more than 40 years of MS research its aetiology remains unknown. This study aims to identify the most frequently reported and consistently regulated molecules in MS in order to generate molecular interaction networks and thereby leading to the identifcation of deregulated processes and pathways which could give an insight of the underlying molecular mechanisms of MS. Driven by an integrative systems biology approach, gene-expression profling datasets were combined and stratifed into “Non-treated” and “Treated” groups and additionally compared to other disease patterns. Molecular identifers from dataset comparisons were matched to our Multiple Sclerosis database (MuScle; www.padb.org/muscle). From 5079 statistically signifcant molecules, correlation analysis within groups identifed a panel of 16 high-confdence genes unique to the naïve MS phenotype, whereas the “Treated” group refected a common pattern associated with autoimmune disease. Pathway and gene-ontology clustering identifed the Interferon gamma signalling pathway as the most relevant amongst all signifcant molecules, and viral infections as the most likely cause of all down-stream events observed. This hypothesis-free approach revealed the most signifcant molecular events amongst diferent MS phenotypes which can be used for further detailed studies. Multiple sclerosis (MS) is considered the leading cause of non-traumatic disability worldwide in young adults. -
Published Version
PUBLISHED VERSION Feng Yu, Cameron P. Bracken, Katherine A. Pillman, David M. Lawrence, Gregory J. Goodall, David F. Callen, Paul M. Neilsen p53 represses the oncogenic Sno-MiR-28 derived from a SnoRNA PLoS One, 2015; 10(6):e0129190-1-e0129190-20 © 2015 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Originally published at: http://doi.org/10.1371/journal.pone.0129190 PERMISSIONS http://creativecommons.org/licenses/by/4.0/ http://hdl.handle.net/2440/97172 RESEARCH ARTICLE p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA Feng Yu1,2,3, Cameron P. Bracken2,3*, Katherine A. Pillman4,5, David M. Lawrence4,5, Gregory J. Goodall2,3, David F. Callen1,2, Paul M. Neilsen1,2,6 1 Centre for Personalized Cancer Medicine, University of Adelaide, Adelaide, SA, Australia, 2 Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia, 3 Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia, 4 ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia, 5 School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia, 6 Swinburne University of Technology, Kuching, Sarawak, Malaysia * [email protected] Abstract p53 is a master tumour repressor that participates in vast regulatory networks, including OPEN ACCESS feedback loops involving microRNAs (miRNAs) that regulate p53 and that themselves are Citation: Yu F, Bracken CP, Pillman KA, Lawrence direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like DM, Goodall GJ, Callen DF, et al.