Genome-Wide DNA Methylation Dynamics During Epigenetic
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Genomic Imprinting at the Porcine PLAGL1 Locus and the Orthologous Locus in the Human
G C A T T A C G G C A T genes Article Genomic Imprinting at the Porcine PLAGL1 Locus and the Orthologous Locus in the Human Jinsoo Ahn 1 , In-Sul Hwang 2 , Mi-Ryung Park 2, Seongsoo Hwang 2 and Kichoon Lee 1,* 1 Functional Genomics Laboratory, Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA; [email protected] 2 Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Wanju, Jeonbuk 55365, Korea; [email protected] (I.-S.H.); [email protected] (M.-R.P.); [email protected] (S.H.) * Correspondence: [email protected]; Tel.: +1-614-688-7963 Abstract: Implementation of genomic imprinting in mammals often results in cis-acting silencing of a gene cluster and monoallelic expression, which are important for mammalian growth and function. Compared with widely documented imprinting status in humans and mice, current understanding of genomic imprinting in pigs is relatively limited. The objectives of this study were to identify DNA methylation status and allelic expression of alternative spliced isoforms at the porcine PLAGL1 locus and assess the conservation of the locus compared to the orthologous human locus. DNA methylome and transcriptome were constructed using porcine parthenogenetic or biparental control embryos. Using methylome, differentially methylated regions between those embryos were identified. Alternative splicing was identified by differential splicing analysis, and monoallelic expression was examined using single nucleotide polymorphism sites. Moreover, topological boundary regions were identified by analyzing CTCF binding sites and compared with the boundary of human orthologous locus. As a result, it was revealed that the monoallelic expression of the PLAGL1 Citation: Ahn, J.; Hwang, I.-S.; Park, M.-R.; Hwang, S.; Lee, K. -
Expression Pattern of Small Nucleolar RNA Host Genes and Long Non-Coding RNA in X-Rays-Treated Lymphoblastoid Cells
Int. J. Mol. Sci. 2013, 14, 9099-9110; doi:10.3390/ijms14059099 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article Expression Pattern of Small Nucleolar RNA Host Genes and Long Non-Coding RNA in X-rays-Treated Lymphoblastoid Cells M. Ahmad Chaudhry Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, VT 05405, USA; E-Mail: [email protected]; Tel.: +1-802-656-0569; Fax: +1-802-656-2191 Received: 5 March 2013; in revised version: 19 April 2013 / Accepted: 22 April 2013 / Published: 25 April 2013 Abstract: A wide variety of biological effects are induced in cells that are exposed to ionizing radiation. The expression changes of coding mRNA and non-coding micro-RNA have been implicated in irradiated cells. The involvement of other classes of non-coding RNAs (ncRNA), such as small nucleolar RNAs (snoRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs) in cells recovering from radiation-induced damage has not been examined. Thus, we investigated whether these ncRNA were undergoing changes in cells exposed to ionizing radiation. The modulation of ncRNAs expression was determined in human TK6 (p53 positive) and WTK1 (p53 negative) cells. The snoRNA host genes SNHG1, SNHG6, and SNHG11 were induced in TK6 cells. In WTK1 cells, SNHG1 was induced but SNHG6, and SNHG11 were repressed. SNHG7 was repressed in TK6 cells and was upregulated in WTK1 cells. The lncRNA MALAT1 and SOX2OT were induced in both TK6 and WTK1 cells and SRA1 was induced in TK6 cells only. Interestingly, the MIAT and PIWIL1 were not expressed in TK6 cells before or after the ionizing radiation treatment. -
Transcriptome Analysis of Alzheimer's Disease Identifies Links to Cardiovascular Disease
Washington University in St. Louis Washington University Open Scholarship All Computer Science and Engineering Research Computer Science and Engineering Report Number: WUCSE-2008-6 2008-01-01 Transcriptome analysis of Alzheimer's disease identifies links ot cardiovascular disease Monika Ray, Jianhua Ruan, and Weixiong Zhang Follow this and additional works at: https://openscholarship.wustl.edu/cse_research Part of the Computer Engineering Commons, and the Computer Sciences Commons Recommended Citation Ray, Monika; Ruan, Jianhua; and Zhang, Weixiong, "Transcriptome analysis of Alzheimer's disease identifies links ot cardiovascular disease" Report Number: WUCSE-2008-6 (2008). All Computer Science and Engineering Research. https://openscholarship.wustl.edu/cse_research/237 Department of Computer Science & Engineering - Washington University in St. Louis Campus Box 1045 - St. Louis, MO - 63130 - ph: (314) 935-6160. Department of Computer Science & Engineering 2008-6 Transcriptome analysis of Alzheimer's disease identifies links to cardiovascular disease Authors: Monika Ray, Jianhua Ruan, Weixiong Zhang Corresponding Author: [email protected] Type of Report: Other Department of Computer Science & Engineering - Washington University in St. Louis Campus Box 1045 - St. Louis, MO - 63130 - ph: (314) 935-6160 Transcriptome analysis of Alzheimer’s disease identifies links to cardiovascular disease Monika Ray1¤, Jianhua Ruan2¤, Weixiong Zhang1;3 1Washington University School of Engineering, Dept. of Computer Science and Engineering, St. Louis, MO 63130 2University of Texas at San Antonio, Dept. of Computer Science, San Antonio, TX 78249 3Washington University School of Medicine, Dept. of Genetics, St. Louis, MO 63110 Correspondence Email: [email protected] ¤ Co-first authors Abstract Understanding the pathogenesis in the early stages of late-onset Alzheimer’s disease (AD) can help in gaining important mechanistic insights into this devastating neurode- generative disorder. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Association of Paraoxonase-2 Genetic Variation with Serum
ASSOCIATION OF PARAOXONASE-2 GENETIC VARIATION WITH SERUM PARAOXONASE ACTIVITY AND SYSTEMIC LUPUS ERYTHEMATOSUS by Sudeshna Dasgupta B.S., University of Calcutta, India, 2001 M.S., University of Calcutta, India, 2003 Submitted to the Graduate Faculty of Graduate School of Public Health in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2008 UNIVERSITY OF PITTSBURGH Graduate School of Public Health This dissertation was presented by Sudeshna Dasgupta It was defended on November 3rd, 2008 and approved by F. Yesim Demirci M.D., Research Assistant Professor, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh Susan M. Manzi, MD, MPH, Associate Professor, Department of Medicine, School of Medicine and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh Candace M. Kammerer, Ph.D. Associate Professor, Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Committee Chair Person Robert E. Ferrell, Ph.D. Professor, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh Dissertation Advisor, M. Ilyas Kamboh, Ph.D. Professor and Chair, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh ii Dedicated to my mother Mrs. Susmita Dasgupta and my father Dr. Gautam Dasgupta iii Copyright © by Sudeshna Dasgupta 2008 iv M. Ilyas Kamboh PhD ASSOCIATION OF PARAOXONASE-2 GENETIC VARIATION WITH SERUM PARAOXONASE ACTIVITY AND SYSTEMIC LUPUS ERYTHEMATOSUS Sudeshna Dasgupta, PhD University of Pittsburgh, 2008 SLE, a severe autoimmune disease is of major public health relevance since it predominantly affects women at child bearing age and even though immunosuppressives have increased the life span of SLE patients, lack of absolute cure is still troubling. -
Zinc-Finger Protein 471 Suppresses Gastric Cancer Through
Oncogene (2018) 37:3601–3616 https://doi.org/10.1038/s41388-018-0220-5 ARTICLE Zinc-finger protein 471 suppresses gastric cancer through transcriptionally repressing downstream oncogenic PLS3 and TFAP2A 1 1 1 2 1 3 Lei Cao ● Shiyan Wang ● Yanquan Zhang ● Ka-Chun Wong ● Geicho Nakatsu ● Xiaohong Wang ● 1 3 1 Sunny Wong ● Jiafu Ji ● Jun Yu Received: 28 June 2017 / Revised: 23 December 2017 / Accepted: 23 February 2018 / Published online: 3 April 2018 © The Author(s) 2018. This article is published with open access Abstract Zinc-finger protein 471 (ZNF471) was preferentially methylated in gastric cancer using promoter methylation array. The role of ZNF471 in human cancer is unclear. Here we elucidated the functional significance, molecular mechanisms and clinical impact of ZNF471 in gastric cancer. ZNF471 mRNA was silenced in 15 out of 16 gastric cancer cell lines due to promoter hypermethylation. Significantly higher ZNF471 promoter methylation was also observed in primary gastric cancers compared to their adjacent normal tissues (P<0.001). ZNF471 promoter CpG-site hypermethylation correlated with poor 1234567890();,: survival of gastric cancer patients (n = 120, P = 0.001). Ectopic expression of ZNF471 in gastric cancer cell lines (AGS, BGC823, and MKN74) significantly suppressed cell proliferation, migration, and invasion, while it induced apoptosis in vitro and inhibited xenograft tumorigenesis in nude mice. Transcription factor AP-2 Alpha (TFAP2A) and plastin3 (PLS3) were two crucial downstream targets of ZNF471 demonstrated by bioinformatics modeling and ChIP-PCR assays. ZNF471 directly bound to the promoter of TFAP2A and PLS3 and transcriptionally inhibited their expression. TFAP2A and PLS3 showed oncogenic functions in gastric cancer cell lines. -
Role of RUNX1 in Aberrant Retinal Angiogenesis Jonathan D
Page 1 of 25 Diabetes Identification of RUNX1 as a mediator of aberrant retinal angiogenesis Short Title: Role of RUNX1 in aberrant retinal angiogenesis Jonathan D. Lam,†1 Daniel J. Oh,†1 Lindsay L. Wong,1 Dhanesh Amarnani,1 Cindy Park- Windhol,1 Angie V. Sanchez,1 Jonathan Cardona-Velez,1,2 Declan McGuone,3 Anat O. Stemmer- Rachamimov,3 Dean Eliott,4 Diane R. Bielenberg,5 Tave van Zyl,4 Lishuang Shen,1 Xiaowu Gai,6 Patricia A. D’Amore*,1,7 Leo A. Kim*,1,4 Joseph F. Arboleda-Velasquez*1 Author affiliations: 1Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford St., Boston, MA 02114 2Universidad Pontificia Bolivariana, Medellin, Colombia, #68- a, Cq. 1 #68305, Medellín, Antioquia, Colombia 3C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114 4Retina Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles St., Boston, MA 02114 5Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115 6Center for Personalized Medicine, Children’s Hospital Los Angeles, Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA 7Department of Pathology, Harvard Medical School, 25 Shattuck St., Boston, MA 02115 Corresponding authors: Joseph F. Arboleda-Velasquez: [email protected] Ph: (617) 912-2517 Leo Kim: [email protected] Ph: (617) 912-2562 Patricia D’Amore: [email protected] Ph: (617) 912-2559 Fax: (617) 912-0128 20 Staniford St. Boston MA, 02114 † These authors contributed equally to this manuscript Word Count: 1905 Tables and Figures: 4 Diabetes Publish Ahead of Print, published online April 11, 2017 Diabetes Page 2 of 25 Abstract Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world’s working adult population, and affects those with type 1 and type 2 diabetes mellitus. -
Targeting PH Domain Proteins for Cancer Therapy
The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 12-2018 Targeting PH domain proteins for cancer therapy Zhi Tan Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Bioinformatics Commons, Medicinal Chemistry and Pharmaceutics Commons, Neoplasms Commons, and the Pharmacology Commons Recommended Citation Tan, Zhi, "Targeting PH domain proteins for cancer therapy" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 910. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/910 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. TARGETING PH DOMAIN PROTEINS FOR CANCER THERAPY by Zhi Tan Approval page APPROVED: _____________________________________________ Advisory Professor, Shuxing Zhang, Ph.D. _____________________________________________ -
Characterization of Dysregulated Lncrna-Mrna Network Based on Cerna Hypothesis to Reveal the Occurrence and Recurrence of Myocar
Zhang et al. Cell Death Discovery (2018) 4:35 DOI 10.1038/s41420-018-0036-7 Cell Death Discovery ARTICLE Open Access Characterization of dysregulated lncRNA- mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction Guangde Zhang1,HaoranSun2, Yawei Zhang2, Hengqiang Zhao2, Wenjing Fan1,JianfeiLi3,YingliLv2, Qiong Song2, Jiayao Li2,MingyuZhang1 and Hongbo Shi2 Abstract Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on “ceRNA hypothesis”. We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions. The constructed DLMN_MI_OC and DLMN_MI_Re both exhibited biological network characteristics, and functional analysis demonstrated that the networks were specific for MI. Additionally, we identified some lncRNA-mRNA ceRNA modules involved in MI occurrence and recurrence. Finally, two new panel biomarkers defined by four lncRNAs (RP1-239B22.5, AC135048.13, RP11-4O1.2, RP11-285F7.2) from 1234567890():,; 1234567890():,; DLMN_MI_OC and three lncRNAs (RP11-363E7.4, CTA-29F11.1, RP5-894A10.6) from DLMN_MI_Re with high classification performance were, respectively, identified in distinguishing controls from patients, and patients with recurrent events from those without recurrent events. This study will provide us new insight into ceRNA-mediated regulatory mechanisms involved in MI occurrence and recurrence, and facilitate the discovery of candidate diagnostic and prognosis biomarkers for MI. -
Germline Mutations Causing Familial Lung Cancer
Journal of Human Genetics (2015) 60, 597–603 & 2015 The Japan Society of Human Genetics All rights reserved 1434-5161/15 www.nature.com/jhg ORIGINAL ARTICLE Germline mutations causing familial lung cancer Koichi Tomoshige1,2, Keitaro Matsumoto1, Tomoshi Tsuchiya1, Masahiro Oikawa1, Takuro Miyazaki1, Naoya Yamasaki1, Hiroyuki Mishima2, Akira Kinoshita2, Toru Kubo3, Kiyoyasu Fukushima3, Koh-ichiro Yoshiura2 and Takeshi Nagayasu1 Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic ‘candidate’ mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer. -
The Role of Cdep in the Embryonic Morphogenesis of Drosophila Melanogaster
The Role of Cdep in the Embryonic Morphogenesis of Drosophila melanogaster Dissertation zur Erlangung des akademischen Grades Doctor rerum naturalium (Dr. rer.nat.) vorgelegt der Fakultät Mathematik und Naturwissenschaften der Technischen Universität Dresden von Anne Morbach Geboren am 05. August 1984 in Nordhausen, Deutschland Eingereicht am 30. Oktober 2015 Die Dissertation wurde in der Zeit von April 2012 bis Oktober 2015 im Max-Planck-Institut für molekulare Zellbiologie und Genetik angefertigt Gutachter: Prof. Dr. Elisabeth Knust Prof. Dr. Christian Dahmann Now, here, you see, it takes all the running you can do, to keep in the same place. Lewis Carroll, Through the Looking-Glass I Contents List of Figures V List of Tables VII Abstract IX List of Abbreviations XI 1 Introduction 1 1.1 Epithelial cell polarity . 1 1.1.1 Cellularization and formation of the primary epithelium . 1 1.1.1.1 Establishment of epithelial polarity and adhesion . 2 1.1.2 The epithelial polarity network . 3 1.1.3 Cell-cell adhesion . 5 1.1.3.1 Adherens junctions . 5 1.1.3.2 Septate junctions . 6 1.2 Epithelial movements in Drosophila embryonic morphogenesis . 6 1.2.1 Epithelial tube formation during Drosophila embryogenesis . 7 1.2.2 Coordinated migration of epithelial sheets during Dros. embryogenesis 7 1.2.2.1 FERM domain proteins in epithelial migration . 9 1.2.2.2 Cdep . 10 1.3 Mutagenesis with the CRISPR/Cas9 system . 12 2 Aim of My PhD Thesis Work 15 3 Preliminary Work 17 4 Results 19 4.1 A screen for novel regulators in Drosophila embryonic morphogenesis . -
Xenopus Piwi Proteins Interact with a Broad Proportion of the Oocyte Transcriptome
Downloaded from rnajournal.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Xenopus Piwi proteins interact with a broad proportion of the oocyte transcriptome JAMES A. TOOMBS,1,2,4 YULIYA A. SYTNIKOVA,3,5 GUNG-WEI CHIRN,3,6 IGNATIUS ANG,3,7 NELSON C. LAU,3 and MICHAEL D. BLOWER1,2 1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA 2Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA 3Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts 02454, USA ABSTRACT Piwi proteins utilize small RNAs (piRNAs) to recognize target transcripts such as transposable elements (TE). However, extensive piRNA sequence diversity also suggests that Piwi/piRNA complexes interact with many transcripts beyond TEs. To determine Piwi target RNAs, we used ribonucleoprotein-immunoprecipitation (RIP) and cross-linking and immunoprecipitation (CLIP) to identify thousands of transcripts associated with the Piwi proteins XIWI and XILI (Piwi-protein-associated transcripts, PATs) from early stage oocytes of X. laevis and X. tropicalis. Most PATs associate with both XIWI and XILI and include transcripts of developmentally important proteins in oogenesis and embryogenesis. Only a minor fraction of PATs in both frog species displayed near perfect matches to piRNAs. Since predicting imperfect pairing between all piRNAs and target RNAs remains intractable, we instead determined that PAT read counts correlate well with the lengths and expression levels of transcripts, features that have also been observed for oocyte mRNAs associated with Drosophila Piwi proteins. We used an in vitro assay with exogenous RNA to confirm that XIWI associates with RNAs in a length- and concentration-dependent manner.