Sox2-RNA Mechanisms of Chromosome Topological Control in Developing Forebrain
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Statistical Analysis of the Genomic Distribution and Correlation of Regulatory Elements in the ENCODE Regions
Downloaded from genome.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Statistical analysis of the genomic distribution and correlation of regulatory elements in the ENCODE regions Zhengdong D. Zhang,1 Alberto Paccanaro,2 Yutao Fu,3 Sherman Weissman,5 Zhiping Weng,3,4 Joseph Chang,6 Michael Snyder,7 and Mark B. Gerstein1,8,9 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA; 2Department of Computer Science Royal Holloway, University of London, Egham Hill, TW20 0EX, United Kingdom; 3Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA; 4Biomedical Engineering Department, Boston University, Boston, Massachusetts 02215, USA; 5Department of Genetics, Yale University, New Haven, Connecticut 06510, USA; 6Department of Statistics, Yale University, New Haven, Connecticut 06520, USA; 7Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA; 8Program in Computational Biology and Bioinformatics Yale University, New Haven, Connecticut 06520, USA The comprehensive inventory of functional elements in 44 human genomic regions carried out by the ENCODE Project Consortium enables for the first time a global analysis of the genomic distribution of transcriptional regulatory elements. In this study we developed an intuitive and yet powerful approach to analyze the distribution of regulatory elements found in many different ChIP–chip experiments on a 10∼100-kb scale. First, we focus on the overall chromosomal distribution of regulatory elements in the ENCODE regions and show that it is highly nonuniform. We demonstrate, in fact, that regulatory elements are associated with the location of known genes. Further examination on a local, single-gene scale shows an enrichment of regulatory elements near both transcription start and end sites. -
Molecular Basis for the Distinct Cellular Functions of the Lsm1-7 and Lsm2-8 Complexes
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.22.055376; this version posted April 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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-ND 4.0 International license. Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes Eric J. Montemayor1,2, Johanna M. Virta1, Samuel M. Hayes1, Yuichiro Nomura1, David A. Brow2, Samuel E. Butcher1 1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. 2Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Correspondence should be addressed to E.J.M. ([email protected]) and S.E.B. ([email protected]). Abstract Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1-7 complex initiates mRNA decay, while the nuclear Lsm2-8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2-8 bound to RNA identify the unique 2′,3′ cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1-7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. -
High Throughput Circrna Sequencing Analysis Reveals Novel Insights Into
Xiong et al. Cell Death and Disease (2019) 10:658 https://doi.org/10.1038/s41419-019-1890-9 Cell Death & Disease ARTICLE Open Access High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma Dan-dan Xiong1, Zhen-bo Feng1, Ze-feng Lai2,YueQin2, Li-min Liu3,Hao-xuanFu2, Rong-quan He4,Hua-yuWu5, Yi-wu Dang1, Gang Chen 1 and Dian-zhong Luo1 Abstract Nitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validated by real-time quantitative polymerase chain reaction. The in vitro experiments showed that the two circRNAs inhibited the malignant biological behaviour of HCC, suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs function as “miRNA sponges” in HCC, we identified circRNA-miRNA and miRNA-mRNA interactions by using the CircInteractome and miRwalk, respectively. Subsequently, 857 miRNA-associated differently expressed genes in HCC were selected for weighted gene co-expression network analysis. Module Eigengene turquoise with 423 genes was found to be significantly related to the survival time, pathology grade and TNM stage of HCC patients. Gene functional enrichment 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; analysis showed that the 423 genes mainly functioned in DNA replication- and cell cycle-related biological processes and signalling cascades. -
Posters A.Pdf
INVESTIGATING THE COUPLING MECHANISM IN THE E. COLI MULTIDRUG TRANSPORTER, MdfA, BY FLUORESCENCE SPECTROSCOPY N. Fluman, D. Cohen-Karni, E. Bibi Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel In bacteria, multidrug transporters couple the energetically favored import of protons to export of chemically-dissimilar drugs (substrates) from the cell. By this function, they render bacteria resistant against multiple drugs. In this work, fluorescence spectroscopy of purified protein is used to unravel the mechanism of coupling between protons and substrates in MdfA, an E. coli multidrug transporter. Intrinsic fluorescence of MdfA revealed that binding of an MdfA substrate, tetraphenylphosphonium (TPP), induced a conformational change in this transporter. The measured affinity of MdfA-TPP was increased in basic pH, raising a possibility that TPP might bind tighter to the deprotonated state of MdfA. Similar increases in affinity of TPP also occurred (1) in the presence of the substrate chloramphenicol, or (2) when MdfA is covalently labeled by the fluorophore monobromobimane at a putative chloramphenicol interacting site. We favor a mechanism by which basic pH, chloramphenicol binding, or labeling with monobromobimane, all induce a conformational change in MdfA, which results in deprotonation of the transporter and increase in the affinity of TPP. PHENOTYPE CHARACTERIZATION OF AZOSPIRILLUM BRASILENSE Sp7 ABC TRANSPORTER (wzm) MUTANT A. Lerner1,2, S. Burdman1, Y. Okon1,2 1Department of Plant Pathology and Microbiology, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot, Israel, 2The Otto Warburg Center for Agricultural Biotechnology, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot, Israel Azospirillum, a free-living nitrogen fixer, belongs to the plant growth promoting rhizobacteria (PGPR), living in close association with plant roots. -
Integrated Genomic Approaches Identify Upregulation of SCRN1 As A
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 12 Integrated genomic approaches identify upregulation of SCRN1 as a novel mechanism associated with acquired resistance to erlotinib in PC9 cells harboring oncogenic EGFR mutation Nayoung Kim1,2, Ahye Cho2, Hideo Watanabe3,4, Yoon-La Choi2,5, Meraj Aziz6, Michelle Kassner6, Je-Gun Joung7, Angela Kyung-Joo Park1,2, Joshua M. Francis8, Joon Seol Bae7, Soo-min Ahn5, Kyoung-Mee Kim5, Joon Oh Park9, Woong-Yang Park2,7, Myung-Ju Ahn9, Keunchil Park9, Jaehyung Koo10, Hongwei Holly Yin6, Jeonghee Cho1,2,7 1Department of NanoBio Medical Science, Dankook University, Cheonan 31116, Republic of Korea 2Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 135-967, Republic of Korea 3Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York, NY 10029, USA 4Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA 5 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-967, Republic of Korea 6 Cancer and Cell Biology Division, Translational Genomics Research Institute, Scottsdale, AZ 85259, USA 7Samsung Genome Institute, Samsung Medical Center, Seoul 135-967, Republic of Korea 8Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA 9 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-967, Republic of Korea 10Department of Brain and Cognitive Sciences, DGIST, Daegu 42988, Republic of Korea Correspondence to: Jeonghee Cho, e-mail: [email protected] Keywords: EGFR, SCRN1, lung adenocarcinoma, erlotinib resistance Received: July 24, 2015 Accepted: January 27, 2016 Published: February 11, 2016 ABSTRACT Therapies targeting the tyrosine kinase activity of Epidermal Growth Factor Receptor (EGFR) have been proven to be effective in treating a subset of non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations. -
Proteomics Provides Insights Into the Inhibition of Chinese Hamster V79
www.nature.com/scientificreports OPEN Proteomics provides insights into the inhibition of Chinese hamster V79 cell proliferation in the deep underground environment Jifeng Liu1,2, Tengfei Ma1,2, Mingzhong Gao3, Yilin Liu4, Jun Liu1, Shichao Wang2, Yike Xie2, Ling Wang2, Juan Cheng2, Shixi Liu1*, Jian Zou1,2*, Jiang Wu2, Weimin Li2 & Heping Xie2,3,5 As resources in the shallow depths of the earth exhausted, people will spend extended periods of time in the deep underground space. However, little is known about the deep underground environment afecting the health of organisms. Hence, we established both deep underground laboratory (DUGL) and above ground laboratory (AGL) to investigate the efect of environmental factors on organisms. Six environmental parameters were monitored in the DUGL and AGL. Growth curves were recorded and tandem mass tag (TMT) proteomics analysis were performed to explore the proliferative ability and diferentially abundant proteins (DAPs) in V79 cells (a cell line widely used in biological study in DUGLs) cultured in the DUGL and AGL. Parallel Reaction Monitoring was conducted to verify the TMT results. γ ray dose rate showed the most detectable diference between the two laboratories, whereby γ ray dose rate was signifcantly lower in the DUGL compared to the AGL. V79 cell proliferation was slower in the DUGL. Quantitative proteomics detected 980 DAPs (absolute fold change ≥ 1.2, p < 0.05) between V79 cells cultured in the DUGL and AGL. Of these, 576 proteins were up-regulated and 404 proteins were down-regulated in V79 cells cultured in the DUGL. KEGG pathway analysis revealed that seven pathways (e.g. -
Somatic Mutation of PIK3CA (H1047R) Is a Common Driver Mutation Hotspot in Canine Mammary Tumors As Well As Human Breast Cancers
cancers Article Somatic Mutation of PIK3CA (H1047R) Is a Common Driver Mutation Hotspot in Canine Mammary Tumors as Well as Human Breast Cancers 1, 1, 2 1 1, Kang-Hoon Lee y, Hyeon-Ji Hwang y, Hyun Ji Noh , Tae-Jin Shin and Je-Yoel Cho * 1 Department of Biochemistry, BK21 Plus and Research Institute for Veterinary Science, School of Veterinary Medicine, Seoul National University, Seoul 08826, Korea; [email protected] (K.-H.L.); [email protected] (H.-J.H.); [email protected] (T.-J.S.) 2 Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; [email protected] * Correspondence: [email protected]; Tel.: +82-02-880-1268 These authors contributed equally to this work. y Received: 7 November 2019; Accepted: 10 December 2019; Published: 12 December 2019 Abstract: Breast cancer is one of the most frequently diagnosed cancers in both women and female dogs. Genome-wide association studies in human breast cancer (HBC) have identified hundreds of genetic variations and somatic driver mutations. However, only a handful of variants have been studied for rare HBC and their associations remain inconclusive. Spontaneous canine mammary tumor (CMT) is a great model for HBC, with clinical similarity. We thus performed whole-exome sequencing in 20 pairs of CMT and normal tissues in dogs. We newly found that PIK3CA was the most frequently mutated gene in CMT (45%). Furthermore, canine PIK3CA A3140G (H1047R), at what is known as the mutational hotspot of HBC, is also a hotspot in CMT. Targeted sequencing confirmed that 29% of CMTs had the same PIK3CA A3140G mutation. -
Mapping of Leptin and Its Syntenic Genes to Chicken Chromosome
Edinburgh Research Explorer Mapping of leptin and its syntenic genes to chicken chromosome 1p Citation for published version: Seroussi, E, Pitel, F, Leroux, S, Morisson, M, Bornelöv, S, Miyara, S, Yosefi, S, Cogburn, LA, Burt, DW, Anderson, L & Friedman-Einat, M 2017, 'Mapping of leptin and its syntenic genes to chicken chromosome 1p', BMC Genetics, vol. 18, no. 1, pp. 77. https://doi.org/10.1186/s12863-017-0543-1 Digital Object Identifier (DOI): 10.1186/s12863-017-0543-1 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: BMC Genetics General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 07. Oct. 2021 Seroussi et al. BMC Genetics (2017) 18:77 DOI 10.1186/s12863-017-0543-1 RESEARCHARTICLE Open Access Mapping of leptin and its syntenic genes to chicken chromosome 1p Eyal Seroussi1*, Frédérique Pitel2, Sophie Leroux2, Mireille Morisson2, Susanne Bornelöv3, Shoval Miyara1, Sara Yosefi1, Larry A. Cogburn4, David W. Burt5, Leif Anderson3,6,7 and Miriam Friedman-Einat1* Abstract Background: Misidentification of the chicken leptin gene has hampered research of leptin signaling in this species for almost two decades. -
Nucleolin and Its Role in Ribosomal Biogenesis
NUCLEOLIN: A NUCLEOLAR RNA-BINDING PROTEIN INVOLVED IN RIBOSOME BIOGENESIS Inaugural-Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf vorgelegt von Julia Fremerey aus Hamburg Düsseldorf, April 2016 2 Gedruckt mit der Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf Referent: Prof. Dr. A. Borkhardt Korreferent: Prof. Dr. H. Schwender Tag der mündlichen Prüfung: 20.07.2016 3 Die vorgelegte Arbeit wurde von Juli 2012 bis März 2016 in der Klinik für Kinder- Onkologie, -Hämatologie und Klinische Immunologie des Universitätsklinikums Düsseldorf unter Anleitung von Prof. Dr. A. Borkhardt und in Kooperation mit dem ‚Laboratory of RNA Molecular Biology‘ an der Rockefeller Universität unter Anleitung von Prof. Dr. T. Tuschl angefertigt. 4 Dedicated to my family TABLE OF CONTENTS 5 TABLE OF CONTENTS TABLE OF CONTENTS ............................................................................................... 5 LIST OF FIGURES ......................................................................................................10 LIST OF TABLES .......................................................................................................12 ABBREVIATION .........................................................................................................13 ABSTRACT ................................................................................................................19 ZUSAMMENFASSUNG -
Gene Expression Profile of Metastatic Human Pancreatic Cancer Cells Depends on the Organ Microenvironment Toru Nakamura,1 Isaiah J
Research Article Gene Expression Profile of Metastatic Human Pancreatic Cancer Cells Depends on the Organ Microenvironment Toru Nakamura,1 Isaiah J. Fidler,1 and Kevin R. Coombes2 Departments of 1Cancer Biology and 2Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Abstract in vitro as monolayer cultures. Although easy to accomplish, To determine the influence of the microenvironment on monolayer cultures are not subjected to any cross talk (e.g., changes in gene expression, we did microarray analysis on paracrine signaling pathways associated with growth in vivo; three variant lines of a human pancreatic cancer (FG, L3.3, ref. 5). Clinical observations of cancer patients and studies in and L3.6pl) with different metastatic potentials. The variant rodent models of cancers have concluded that certain tumors tend lines were grown in tissue culture in the subcutis (ectopic) or to metastasize to certain organs (6). The concept that metastasis pancreas (orthotopic) of nude mice. Compared with tissue results only when certain tumor cells interact with a specific culture, the number of genes of which the expression was organ microenvironment was originally proposed in Paget’s affected by the microenvironment was up-regulated in tumors venerable ‘‘seed and soil’’ hypothesis (7). Indeed, spontaneous metastasis is produced by tumors growing at orthotopic sites, growing in the subcutis and pancreas. In addition, highly metastatic L3.6pl cells growing in the pancreas expressed whereas the same tumor cells implanted into ectopic sites fail to significantly higher levels of 226 genes than did the L3.3 or produce metastasis (8). -
The Landscape of Genomic Imprinting Across Diverse Adult Human Tissues
Downloaded from genome.cshlp.org on September 30, 2021 - Published by Cold Spring Harbor Laboratory Press Research The landscape of genomic imprinting across diverse adult human tissues Yael Baran,1 Meena Subramaniam,2 Anne Biton,2 Taru Tukiainen,3,4 Emily K. Tsang,5,6 Manuel A. Rivas,7 Matti Pirinen,8 Maria Gutierrez-Arcelus,9 Kevin S. Smith,5,10 Kim R. Kukurba,5,10 Rui Zhang,10 Celeste Eng,2 Dara G. Torgerson,2 Cydney Urbanek,11 the GTEx Consortium, Jin Billy Li,10 Jose R. Rodriguez-Santana,12 Esteban G. Burchard,2,13 Max A. Seibold,11,14,15 Daniel G. MacArthur,3,4,16 Stephen B. Montgomery,5,10 Noah A. Zaitlen,2,19 and Tuuli Lappalainen17,18,19 1The Blavatnik School of Computer Science, Tel-Aviv University, Tel Aviv 69978, Israel; 2Department of Medicine, University of California San Francisco, San Francisco, California 94158, USA; 3Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; 4Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA; 5Department of Pathology, Stanford University, Stanford, California 94305, USA; 6Biomedical Informatics Program, Stanford University, Stanford, California 94305, USA; 7Wellcome Trust Center for Human Genetics, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom; 8Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland; 9Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; -
WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT (51) International Patent Classification: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, C12Q 1/68 (2018.01) A61P 31/18 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, C12Q 1/70 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2018/056167 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 16 October 2018 (16. 10.2018) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 62/573,025 16 October 2017 (16. 10.2017) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, ΓΕ , IS, IT, LT, LU, LV, (71) Applicant: MASSACHUSETTS INSTITUTE OF MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TECHNOLOGY [US/US]; 77 Massachusetts Avenue, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Cambridge, Massachusetts 02139 (US).