Integrative Networks in Intellectual Disabilities
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CHD4/Nurd Complex Regulates Complement Gene Expression And
Shao et al. Clinical Epigenetics (2020) 12:31 https://doi.org/10.1186/s13148-020-00827-3 RESEARCH Open Access CHD4/NuRD complex regulates complement gene expression and correlates with CD8 T cell infiltration in human hepatocellular carcinoma Simin Shao1†, Haowei Cao1†, Zhongkun Wang1, Dongmei Zhou2, Chaoshen Wu1, Shu Wang1, Dian Xia1 and Daoyong Zhang1* Abstract Backgrounds: The NuRD (Nucleosome Remodeling and Deacetylation) complex is a repressive complex in gene transcription by modulating chromatin accessibility of target genes to transcription factors and RNA polymerase II. Although individual subunits of the complex have been implicated in many other cancer types, the complex’s role in human hepatocellular carcinoma (HCC) is not fully understood. More importantly, the NuRD complex has not yet been investigated as a whole in cancers. Methods: We analyzed the expression of the NuRD complex in HCC and evaluated the prognostic value of NuRD complex expression in HCC using the RNA-seq data obtained from the TCGA project. We examined the effect of CHD4 knockdown on HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition, colony-forming ability, and on complement gene expression. We also performed bioinformatic analyses to investigate the correlation between the NuRD complex expression and immune infiltration. Results: We found that nine subunits, out of 14 subunits of the NuRD complex examined, were significantly overexpressed in HCC, and their expression levels were positively correlated with cancer progression. More importantly, our data also demonstrated that these subunits tended to be overexpressed as a whole in HCC. Subsequent studies demonstrated that knockdown of CHD4 in HCC cells inhibits cell proliferation, migration, invasion, and colony-forming ability and promotes apoptosis of HCC cells, indicating that the CHD4/NuRD complex plays oncogenic roles in HCC. -
Cyclin D1 Is a Direct Transcriptional Target of GATA3 in Neuroblastoma Tumor Cells
Oncogene (2010) 29, 2739–2745 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 $32.00 www.nature.com/onc SHORT COMMUNICATION Cyclin D1 is a direct transcriptional target of GATA3 in neuroblastoma tumor cells JJ Molenaar1,2, ME Ebus1, J Koster1, E Santo1, D Geerts1, R Versteeg1 and HN Caron2 1Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and 2Department of Pediatric Oncology, Emma Kinderziekenhuis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Almost all neuroblastoma tumors express excess levels of 2000). Several checkpoints normally prevent premature Cyclin D1 (CCND1) compared to normal tissues and cell-cycle progression and cell division. The crucial G1 other tumor types. Only a small percentage of these entry point is controlled by the D-type Cyclins that can neuroblastoma tumors have high-level amplification of the activate CDK4/6 that in turn phosphorylate the pRb Cyclin D1 gene. The other neuroblastoma tumors have protein. This results in a release of the E2F transcription equally high Cyclin D1 expression without amplification. factor that causes transcriptional upregulation of Silencing of Cyclin D1 expression was previously found to numerous genes involved in further progression of the trigger differentiation of neuroblastoma cells. Over- cell cycle (Sherr, 1996). expression of Cyclin D1 is therefore one of the most Neuroblastomas are embryonal tumors that originate frequent mechanisms with a postulated function in neuro- from precursor cells of the sympathetic nervous system. blastoma pathogenesis. The cause for the Cyclin D1 This tumor has a very poor prognosis and despite the overexpression is unknown. -
Adaptive Tuning of Mutation Rates Allows Fast Response to Lethal Stress In
Manuscript 1 Adaptive tuning of mutation rates allows fast response to lethal stress in 2 Escherichia coli 3 4 a a a a a,b 5 Toon Swings , Bram Van den Bergh , Sander Wuyts , Eline Oeyen , Karin Voordeckers , Kevin J. a,b a,c a a,* 6 Verstrepen , Maarten Fauvart , Natalie Verstraeten , Jan Michiels 7 8 a 9 Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Kasteelpark Arenberg 20, 10 3001 Leuven, Belgium b 11 VIB Laboratory for Genetics and Genomics, Vlaams Instituut voor Biotechnologie (VIB) Bioincubator 12 Leuven, Gaston Geenslaan 1, 3001 Leuven, Belgium c 13 Smart Systems and Emerging Technologies Unit, imec, Kapeldreef 75, 3001 Leuven, Belgium * 14 To whom correspondence should be addressed: Jan Michiels, Department of Microbial and 2 15 Molecular Systems (M S), Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, box 16 2460, 3001 Leuven, Belgium, [email protected], Tel: +32 16 32 96 84 1 Manuscript 17 Abstract 18 19 While specific mutations allow organisms to adapt to stressful environments, most changes in an 20 organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often 21 considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in 22 cellular mutation rates as a response to changes in selective pressure. We show that hypermutation 23 independently evolves when different Escherichia coli cultures adapt to high ethanol stress. 24 Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation 25 rate. Specifically, population mutation rates rise when cells experience higher stress and decline again 26 once cells are adapted. -
The Gene Repressor Complex Nurd Interacts with the Histone Variant H3.3
Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press The gene repressor complex NuRD interacts with the histone variant H3.3 at promoters of active genes Daniel C. Kraushaar1,3,4, Zuozhou Chen2,4, Qingsong Tang1, Kairong Cui1, Junfang Zhang2,*, Keji Zhao1,* 1 Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, MD 2 Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China. 3 Current address: Genomic and RNA Profiling Core, Baylor College of Medicine, TX 4These authors contributed equally to this work *Correspondence: Junfang Zhang ([email protected]); Keji Zhao ([email protected]) Key words: histone variant H3.3; chromatin modification; epigenetics; ChIP-seq; protein interaction; NuRD; histone modification 1 Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract The histone variant H3.3 is deposited across active genes, regulatory regions and telomeres. It remains unclear how H3.3 interacts with chromatin modifying enzymes and thereby modulates gene activity. In this study, we performed a co- immunoprecipitation-mass spectrometry analysis of proteins associated with H3.3-containing nucleosomes and identified the Nucleosome Remodeling and Deacetylase complex (NuRD) as a major H3.3-interactor. We show that the H3.3- NuRD interaction is dependent on the H3.3 lysine 4 residue and that NuRD binding occurs when lysine 4 is in its unmodified state. -
Dynamic Mutations on the Move
9789 Mled Genet 1993; 30: 978-981 REVIEW ARTICLE J Med Genet: first published as 10.1136/jmg.30.12.978 on 1 December 1993. Downloaded from Dynamic mutations on the move Grant R Sutherland, Robert I Richards It is only a short time since the isolation and quences is rapidly increasing (table). These characterisation of the fragile X syndrome mu- include another fragile site (FRAXE) that may tation'-3 uncovered a new genetic element and be associated with mild mental retardation.'2 mechanism of mutation. The genetic element This fragile site has turned out to be similar in was an unstable DNA sequence resulting from structure to the fragile X (FRAXA), involving amplification of a naturally occurring poly- the same trinucleotide p(CCG)n and being morphic trinucleotide repeat, p(CCG)n. The close to a CpG island which is hypermethy- mechanism of mutation, which we have lated when the copy number exceeds approx- termed dynamic mutation,4 is the change (in- imately 200.* crease or decrease) in copy number of the The dynamic mutations characterised to trinucleotide repeat with the rate of change date fall into two categories probably deter- related to the number of copies present at any mined by whether the trinucleotide repeat is in time. This process, in which an initial change a translated or untranslated region of a gene. to a DNA sequence alters the chance of further The mutations in known or presumed changes to it, contrasts with classical or static untranslated regions, FRAXA, FRAXE, and mutation in which the product of a mutation is DM, appear to have little constraint on the no more likely to undergo further changes than number of repeats, which can range up to was the initial DNA sequence. -
General Contribution
24 Abstracts of 37th Annual Meeting A1 A SCREENING METHOD FOR FRAGILE X MUTATION: DETECTION OF THE CGG REPEAT IN FMR-1 GENE BY PCR WITH BIOTIN-LABELED PRIMER. ..Eiji NANBA, Kousaku OHNO and Kenzo TAKESHITA Division of Child Neurology, Institute of Neurological Sciences, Tot- tori University School of Medicine. Yonago We have developed a new polymerase chain reaction(PCR)-based method for detection of the CGG repeat in FMR-1 gene. No specific product from PCR was detected on the gel with ethidium bromide staining, because 7-deaza-2'-dGTP is necessary for amplification of this repeat. Biotin-labeled primer was used for PCR and the product was transferred to a nylon membrane followed the detection of biotin by Smilight kit. The size of PCR product from normal control were slightly various and around 300bp. No PCR product was detected from 3 fragile X male patients in 2 families diagnosed by cytogenetic examination. This method is useful for genetic screen- ing of male mental retardation patients to exclude the fragile X mutation. A2 DNA ANALYSISFOR FRAGILE X SYNDROME Osamu KOSUDA,Utak00GASA, ~.ideynki INH, a~ji K/NAGIJCltI, and Kazumasa ]tIKIJI (SILL Inc., Tokyo) Fragile X syndrome is X-linked disease having the amplification of (CG6)n repeat sequence in the chromsomeXq27.3. We performed Southern blot analysis using three probes recognized repetitive sequence resion. Normal controle showed 5.2Kb with Eco RI digest and 2.7Kb with Eco RI/Bss ttII digest as the germ tines by the Southern blot analysis. However, three cell lines established fro~ unrelated the patients with fragile X showed the abnormal bands between 5.2 and 7.7Kb with Eco RI digest, and between 2.7 and 7.7Kb with Eco aI/Bss HII digest. -
Supplementary Materials
Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine -
Neutralizing Gatad2a-Chd4-Mbd3 Axis Within the Nurd Complex
bioRxiv preprint doi: https://doi.org/10.1101/192781; this version posted February 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Neutralizing Gatad2a-Chd4-Mbd3 Axis 2 within the NuRD Complex Facilitates 3 Deterministic Induction of Naïve Pluripotency 4 1* 1* 1 1,2 1 5 Nofar Mor , Yoach Rais , Shani Peles , Daoud Sheban , Alejandro Aguilera-Castrejon , 1 3 1 1 1 6 Asaf Zviran , Dalia Elinger , Sergey Viukov , Shay Geula , Vladislav Krupalnik , Mirie 1 4,5 1 1 1 1 7 Zerbib , Elad Chomsky , Lior Lasman , Tom Shani , Jonathan Bayerl , Ohad Gafni , 6 7,8 9 10 10 8 Suhair Hanna , Jason D. Buenrostro , Tzachi Hagai , Hagit Masika , Yehudit Bergman , 11,12 13 3 1 2 9 William J. Greenleaf , Miguel A. Esteban , Yishai Levin , Rada Massarwa , Yifat Merbl , 1#@ 1#@% 10 Noa Novershtern and Jacob H. Hanna . 1 11 The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. 2 12 The Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. 13 3 The Nancy and Stephen Grand Israel National Center for Personalized Medicine (INCPM), 14 Weizmann Institute of Science, Rehovot 7610001, Israel. 15 4 Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel 16 5 Department of Computer Science, Weizmann Institute of Science, Rehovot 7610001, Israel 17 6 Department of Pediatrics and the Pediatric Immunology Unit, Rambam Health Care Campus & 18 Bruce -
Tissue-Specific Dnase I Footprint Analysis Confirms the Association Of
Journal of Genetics (2021)100:61 Ó Indian Academy of Sciences https://doi.org/10.1007/s12041-021-01308-z (0123456789().,-volV)(0123456789().,-volV) Tissue-specific DNase I footprint analysis confirms the association of GATAD2B Q470* variant with intellectual disability VIDYA NIKAM1* and NAUSHAD SHAIK MOHAMMAD2 1Department of Chemistry, Savitribai Phule Pune University, Pune 411 007, India 2Biochemical Genetics, Sandor Speciality Diagnostics, Banjara Hills, Hyderabad 500 034, India *For correspondence. E-mail: [email protected]. Received 8 March 2021; revised 19 April 2021; accepted 4 May 2021 Abstract. Intellectual disability (ID) is a neurodevelopmental disorder in which genetics play a key aetiological role. GATA zinc finger domain-containing 2B (GATAD2B) gene encodes a zinc-finger protein transcriptional repressor which is a part of the methyl-CpG binding protein-1 complex. Pathogenic variants in this gene are linked to ID, dysmorphic features, and cognitive disability. To date, only 18 cases are reported worldwide and only one case is reported from India. A 12-year-old girl presented with a heterozygous nonsense variation in exon 8 of the GATAD2B gene (chr1:153785737G[A). She has severe ID and significant delayed developmental milestones along with clinical features including broad arched eyebrows, low-set ears, a bulbous nose tip, thin upper lip, and wide mouth with downturned corners. This is the second report of a heterozygous mutation in the GATAD2B gene from India with a novel phenotype. To substantiate the association of GATAD2B mutation with ID, we performed DNase I footprint analysis of wild and mutant DNA sequences to establish k-mer binding profile and deduced GATA binding affinity using human ENCODE experimental data of foetal brain. -
Test ID: NGMEM
NEW TEST NOTIFICATION DATE: April 25, 2017 EFFECTIVE DATE: May 15, 2017 RED BLOOD CELL MEMBRANE SEQUENCING, VARIES Test ID: NGMEM USEFUL FOR: Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of an RBC membrane disorder Second-tier testing for patients in whom previous targeted gene mutation analyses were negative for a specific RBC membrane disorder Establishing a diagnosis of a hereditary RBC membrane disorder, allowing for appropriate management and surveillance of disease features based on the gene involved Identifying mutations within genes associated with phenotypic severity, allowing for predictive testing and further genetic counseling METHOD: Hereditary Mutation Detection by Next-Generation Sequencing (NGS) REFERENCE VALUES: An interpretive report will be provided. This next-generation sequencing assay is performed to test for the presence of a mutation in targeted regions of the following 15 genes and intronic regions: ANK1, EPB41, EPB42, GYPC, HBB, HBD, PIEZO1, RHAG, SLC2A1, SLC4A1, SPTA1, SPTB, STOM, UGT1A1, and XK. SPECIMEN REQUIREMENTS: Submit only 1 of the following specimens: Specimen Type: Peripheral blood (preferred) Container/Tube: Preferred: Lavender top (EDTA) or yellow top (ACD) Acceptable: Green top (heparin) Specimen Volume: 3 mL Specimen Stability: Ambient < or =14 days Collection Instructions: 1. Invert several times to mix blood. 2. Send specimen in original tube. 3. Label specimen as blood. Specimen Type: Extracted DNA Container/Tube: 1.5- to 2-mL tube with indication of volume and concentration of the DNA. Specimen Volume: Entire specimen Specimen Stability: Frozen/Refrigerated/Ambient < or =30 days Collection Instructions: Label specimen as extracted DNA and source of specimen. -
Arnau Soler2019.Pdf
This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Genetic responses to environmental stress underlying major depressive disorder Aleix Arnau Soler Doctor of Philosophy The University of Edinburgh 2019 Declaration I hereby declare that this thesis has been composed by myself and that the work presented within has not been submitted for any other degree or professional qualification. I confirm that the work submitted is my own, except where work which has formed part of jointly-authored publications has been included. My contribution and those of the other authors to this work are indicated below. I confirm that appropriate credit has been given within this thesis where reference has been made to the work of others. I composed this thesis under guidance of Dr. Pippa Thomson. Chapter 2 has been published in PLOS ONE and is attached in the Appendix A, chapter 4 and chapter 5 are published in Translational Psychiatry and are attached in the Appendix C and D, and I expect to submit chapter 6 as a manuscript for publication. -
Genome Mapping Resolves Structural Variation Within Segmental Duplications Associated
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.30.071449; this version posted May 2, 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-ND 4.0 International license. 1 Genome mapping resolves structural variation within segmental duplications associated 2 with microdeletion/microduplication syndromes 3 4 Authors 5 Yulia Mostovoy1,*, Feyza Yilmaz2,3,*, Stephen K. Chow1, Catherine Chu1, Chin Lin1, Elizabeth A. 6 Geiger3, Naomi J. L. Meeks3, Kathryn. C. Chatfield3,4, Curtis R. Coughlin II3, Pui-Yan Kwok1,5,6,#, 7 Tamim H. Shaikh3,# 8 9 Affiliations 10 1Cardiovascular Research Institute, UCSF School of Medicine, San Francisco, California 94143, 11 USA 12 2Department of Integrative Biology, University of Colorado Denver, Denver, Colorado 80204, 13 USA 14 3Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado 15 School of Medicine, Aurora, Colorado 80045, USA 16 4Department of Pediatrics, Section of Cardiology, University of Colorado School of Medicine, 17 Aurora, Colorado 80045, USA 18 5Department of Dermatology, and 6Institute for Human Genetics, UCSF School of Medicine, San 19 Francisco, California 94143, USA 20 21 * These two authors contributed equally to the work presented 22 # Address correspondence to: [email protected]; [email protected] 23 24 Running Title 25 Resolving structures within segmental duplications 26 27 Keywords 28 Segmental duplications, genome mapping, structural variation, genomic disorders 29 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.30.071449; this version posted May 2, 2020.