GREAT, a Functional Enrichment Approach and Tool for Interpretation of Genome-Wide Cis-Regulatory Datasets
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The Development of the Mammalian Central
Chapter 5: GRIPE is a novel gene that may assume different roles during development and in adulthood Chapter 5: GRIPE is a novel gene that may assume different roles during development and in adulthood 5.1. Characterisation of GRIPE and E12 mRNA expression during development As a first step towards describing the expression of GRIPE and E12 during neurodevelopment, Northern analysis was conducted to acquire a global pattern of mRNA expression. To do this, embryonic and adult tissues were harvested for RNA isolation as described (Section 2.2). Northern hybridisation was then performed using radiolabelled GRIPE and E12 cDNAs as probes, and these results are shown in Fig. 5.1. A single band of approximately 8kb is detected in all samples; this was the only signal detected in all northern hybridisations performed with different GRIPE cDNA and cRNA probes (see Appendix 10.2). It would appear that GRIPE mRNA is abundant in the head and trunk at e11.5, and levels decrease during embryogenesis, and are undetectable by e17.5. In the adult, GRIPE is abundant in the brain, but is undetectable in the placenta and kidney. However, further RT-PCR experiments (see Figs 6.8 and 6.13) indicate that GRIPE is weakly detectable in these tissues, but not in the kidney. Northern analysis of E12 mRNA shows high levels of expression at e11.5, with a gradual decrease during embryogenesis, and is almost undetectable by e17.5. Further, E12 is undetectable in adult brain, placenta and kidney. These observations demonstrate a coincidence in expression of GRIPE and E12 mRNA during embryogenesis, but not in the adult; where E12 mRNA is undetectable. -
Comparative Transcriptome Profiling of the Human and Mouse Dorsal Root Ganglia: an RNA-Seq-Based Resource for Pain and Sensory Neuroscience Research
bioRxiv preprint doi: https://doi.org/10.1101/165431; this version posted October 13, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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. Title: Comparative transcriptome profiling of the human and mouse dorsal root ganglia: An RNA-seq-based resource for pain and sensory neuroscience research Short Title: Human and mouse DRG comparative transcriptomics Pradipta Ray 1, 2 #, Andrew Torck 1 , Lilyana Quigley 1, Andi Wangzhou 1, Matthew Neiman 1, Chandranshu Rao 1, Tiffany Lam 1, Ji-Young Kim 1, Tae Hoon Kim 2, Michael Q. Zhang 2, Gregory Dussor 1 and Theodore J. Price 1, # 1 The University of Texas at Dallas, School of Behavioral and Brain Sciences 2 The University of Texas at Dallas, Department of Biological Sciences # Corresponding authors Theodore J Price Pradipta Ray School of Behavioral and Brain Sciences School of Behavioral and Brain Sciences The University of Texas at Dallas The University of Texas at Dallas BSB 14.102G BSB 10.608 800 W Campbell Rd 800 W Campbell Rd Richardson TX 75080 Richardson TX 75080 972-883-4311 972-883-7262 [email protected] [email protected] Number of pages: 27 Number of figures: 9 Number of tables: 8 Supplementary Figures: 4 Supplementary Files: 6 Word count: Abstract = 219; Introduction = 457; Discussion = 1094 Conflict of interest: The authors declare no conflicts of interest Patient anonymity and informed consent: Informed consent for human tissue sources were obtained by Anabios, Inc. (San Diego, CA). Human studies: This work was approved by The University of Texas at Dallas Institutional Review Board (MR 15-237). -
Supplementary Table 1
Supplementary Table 1. 492 genes are unique to 0 h post-heat timepoint. The name, p-value, fold change, location and family of each gene are indicated. Genes were filtered for an absolute value log2 ration 1.5 and a significance value of p ≤ 0.05. Symbol p-value Log Gene Name Location Family Ratio ABCA13 1.87E-02 3.292 ATP-binding cassette, sub-family unknown transporter A (ABC1), member 13 ABCB1 1.93E-02 −1.819 ATP-binding cassette, sub-family Plasma transporter B (MDR/TAP), member 1 Membrane ABCC3 2.83E-02 2.016 ATP-binding cassette, sub-family Plasma transporter C (CFTR/MRP), member 3 Membrane ABHD6 7.79E-03 −2.717 abhydrolase domain containing 6 Cytoplasm enzyme ACAT1 4.10E-02 3.009 acetyl-CoA acetyltransferase 1 Cytoplasm enzyme ACBD4 2.66E-03 1.722 acyl-CoA binding domain unknown other containing 4 ACSL5 1.86E-02 −2.876 acyl-CoA synthetase long-chain Cytoplasm enzyme family member 5 ADAM23 3.33E-02 −3.008 ADAM metallopeptidase domain Plasma peptidase 23 Membrane ADAM29 5.58E-03 3.463 ADAM metallopeptidase domain Plasma peptidase 29 Membrane ADAMTS17 2.67E-04 3.051 ADAM metallopeptidase with Extracellular other thrombospondin type 1 motif, 17 Space ADCYAP1R1 1.20E-02 1.848 adenylate cyclase activating Plasma G-protein polypeptide 1 (pituitary) receptor Membrane coupled type I receptor ADH6 (includes 4.02E-02 −1.845 alcohol dehydrogenase 6 (class Cytoplasm enzyme EG:130) V) AHSA2 1.54E-04 −1.6 AHA1, activator of heat shock unknown other 90kDa protein ATPase homolog 2 (yeast) AK5 3.32E-02 1.658 adenylate kinase 5 Cytoplasm kinase AK7 -
Epi)Genomics Data in the 3T9mycer, Eµ-Myc and Tet-MYC
PhD degree in Molecular Medicine (curriculum in Computational Biology) European School of Molecular Medicine (SEMM), University of Milan and University of Naples “Federico II” An integrative approach to identify binding partners of Myc using (epi)genomics data in the 3T9MycER, Eµ-myc and tet-MYC systems Pranami Bora Center for Genomic Science of IIT@SEMM, Milan Matricola n. R10337 Supervisor: Dr. Bruno Amati Center for Genomic Science of IIT@SEMM, Milan Added Supervisor: Dr. Marco Morelli Center for Genomic Science of IIT@SEMM, Milan Anno accademico 2016-2017 Table of Contents List of abbreviations ...................................................................................................... 4 Figures index ................................................................................................................. 5 Abstract ........................................................................................................................ 8 Chapter 1 ..................................................................................................................... 10 Introduction ................................................................................................................. 10 1.1 Epigenetics ............................................................................................................... 10 1.1.1 Acetylation and methylation ..................................................................................... 10 1.1.2 Transcription factors ................................................................................................. -
Novel Genes Upregulated When NOTCH Signalling Is Disrupted During Hypothalamic Development Ratié Et Al
Novel genes upregulated when NOTCH signalling is disrupted during hypothalamic development Ratié et al. Ratié et al. Neural Development 2013, 8:25 http://www.neuraldevelopment.com/content/8/1/25 Ratié et al. Neural Development 2013, 8:25 http://www.neuraldevelopment.com/content/8/1/25 RESEARCH ARTICLE Open Access Novel genes upregulated when NOTCH signalling is disrupted during hypothalamic development Leslie Ratié1, Michelle Ware1, Frédérique Barloy-Hubler1,2, Hélène Romé1, Isabelle Gicquel1, Christèle Dubourg1,3, Véronique David1,3 and Valérie Dupé1* Abstract Background: The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. It is well known that the Notch signalling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. However, the role of Notch during hypothalamus formation along with its downstream effectors remains poorly defined. Results: Here, we have transiently blocked Notch activity in chick embryos and used global gene expression analysis to provide evidence that Notch signalling modulates the generation of neurons in the early developing hypothalamus by lateral inhibition. Most importantly, we have taken advantage of this model to identify novel targets of Notch signalling, such as Tagln3 and Chga, which were expressed in hypothalamic neuronal nuclei. Conclusions: These data give essential advances into the early generation of neurons in the hypothalamus. We demonstrate that inhibition of Notch signalling during early development of the hypothalamus enhances expression of several new markers. These genes must be considered as important new targets of the Notch/proneural network. -
Bioinformatics Analysis of Hereditary Disease Gene Set to Identify Key Modulators of Myocardial Remodeling During Heart Regeneration in Zebrafish
EPiC Series in Computing Volume 70, 2020, Pages 226{237 Proceedings of the 12th International Conference on Bioinformatics and Computational Biology Bioinformatics analysis of hereditary disease gene set to identify key modulators of myocardial remodeling during heart regeneration in zebrafish Lawrence Yu-Min Liu1,2, Zih-Yin Lai1, Min-Hsuan Lin1, Yu Shih3 and Yung-Jen Chuang1 1 Department of Medical Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013, Taiwan 2 Division of Cardiology, Department of Internal Medicine, Hsinchu Mackay Memorial Hospital, Hsinchu, 30071, Taiwan 3 Interdisciplinary Program of Life Science, National Tsing Hua University, Hsinchu, 30013, Taiwan [email protected], [email protected], [email protected], [email protected], [email protected] Abstract Unlike mammals, adult zebrafish hearts retain a remarkable capacity to regenerate after injury. Since regeneration shares many common molecular pathways with embryonic development, we investigated myocardial remodeling genes and pathways by performing a comparative transcriptomic analysis of zebrafish heart regeneration using a set of known human hereditary heart disease genes related to myocardial hypertrophy during development. We cross-matched human hypertrophic cardiomyopathy-associated genes with a time-course microarray dataset of adult zebrafish heart regeneration. Genes in the expression profiles that were highly elevated in the early phases of myocardial repair and remodeling after injury in zebrafish were identified. These genes were further analyzed with web-based bioinformatics tools to construct a regulatory network revealing potential transcription factors and their upstream receptors. In silico functional analysis of these genes showed that they are involved in cardiomyocyte proliferation and differentiation, angiogenesis, and inflammation-related pathways. -
Positional Specificity of Different Transcription Factor Classes Within Enhancers
Positional specificity of different transcription factor classes within enhancers Sharon R. Grossmana,b,c, Jesse Engreitza, John P. Raya, Tung H. Nguyena, Nir Hacohena,d, and Eric S. Landera,b,e,1 aBroad Institute of MIT and Harvard, Cambridge, MA 02142; bDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; cProgram in Health Sciences and Technology, Harvard Medical School, Boston, MA 02215; dCancer Research, Massachusetts General Hospital, Boston, MA 02114; and eDepartment of Systems Biology, Harvard Medical School, Boston, MA 02215 Contributed by Eric S. Lander, June 19, 2018 (sent for review March 26, 2018; reviewed by Gioacchino Natoli and Alexander Stark) Gene expression is controlled by sequence-specific transcription type-restricted enhancers (active in <50% of the cell types) and factors (TFs), which bind to regulatory sequences in DNA. TF ubiquitous enhancers (active in >90% of the cell types) (SI Ap- binding occurs in nucleosome-depleted regions of DNA (NDRs), pendix, Fig. S1C). which generally encompass regions with lengths similar to those We next sought to infer functional TF-binding sites within the protected by nucleosomes. However, less is known about where active regulatory elements. In a recent study (5), we found that within these regions specific TFs tend to be found. Here, we char- TF binding is strongly correlated with the quantitative DNA acterize the positional bias of inferred binding sites for 103 TFs accessibility of a region. Furthermore, the TF motifs associated within ∼500,000 NDRs across 47 cell types. We find that distinct with enhancer activity in reporter assays in a cell type corre- classes of TFs display different binding preferences: Some tend to sponded closely to those that are most enriched in the genomic have binding sites toward the edges, some toward the center, and sequences of active regulatory elements in that cell type (5). -
T-, B-And NK-Lymphoid, but Not Myeloid Cells Arise from Human
Leukemia (2007) 21, 311–319 & 2007 Nature Publishing Group All rights reserved 0887-6924/07 $30.00 www.nature.com/leu ORIGINAL ARTICLE T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34 þ CD38ÀCD7 þ common lymphoid progenitors expressing lymphoid-specific genes I Hoebeke1,3, M De Smedt1, F Stolz1,4, K Pike-Overzet2, FJT Staal2, J Plum1 and G Leclercq1 1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium and 2Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands Hematopoietic stem cells in the bone marrow (BM) give rise to share a direct common progenitor either, as CLPs were not all blood cells. According to the classic model of hematopoi- found in the fetal liver.5 Instead, fetal B and T cells would esis, the differentiation paths leading to the myeloid and develop through B/myeloid and T/myeloid intermediates. lymphoid lineages segregate early. A candidate ‘common 6 lymphoid progenitor’ (CLP) has been isolated from The first report of a human CLP came from Galy et al. who À þ CD34 þ CD38À human cord blood cells based on CD7 expres- showed that a subpopulation of adult and fetal BM Lin CD34 sion. Here, we confirm the B- and NK-differentiation potential of cells expressing the early B- and T-cell marker CD10 is not þ À þ CD34 CD38 CD7 cells and show in addition that this capable of generating monocytic, granulocytic, erythroid or population has strong capacity to differentiate into T cells. As megakaryocytic cells, but can differentiate into dendritic cells, CD34 þ CD38ÀCD7 þ cells are virtually devoid of myeloid B, T and NK cells. -
BMC Genomics Biomed Central
BMC Genomics BioMed Central Research article Open Access Meta-analysis of expression signatures of muscle atrophy: gene interaction networks in early and late stages Enrica Calura1, Stefano Cagnin2, Anna Raffaello2, Paolo Laveder2, Gerolamo Lanfranchi2 and Chiara Romualdi*2 Address: 1Department of Biology, University of Ferrara, Via L. Borsari 46 I-44100 Ferrara, Italy and 2CRIBI Biotechnology Centre and Department of Biology, University of Padova, via U. Bassi 58/B 30121 Padova, Italy Email: Enrica Calura - [email protected]; Stefano Cagnin - [email protected]; Anna Raffaello - [email protected]; Paolo Laveder - [email protected]; Gerolamo Lanfranchi - [email protected]; Chiara Romualdi* - [email protected] * Corresponding author Published: 23 December 2008 Received: 25 April 2008 Accepted: 23 December 2008 BMC Genomics 2008, 9:630 doi:10.1186/1471-2164-9-630 This article is available from: http://www.biomedcentral.com/1471-2164/9/630 © 2008 Calura et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Skeletal muscle mass can be markedly reduced through a process called atrophy, as a consequence of many diseases or critical physiological and environmental situations. Atrophy is characterised by loss of contractile proteins and reduction of fiber volume. Although in the last decade the molecular aspects underlying muscle atrophy have received increased attention, the fine mechanisms controlling muscle degeneration are still incomplete. In this study we applied meta- analysis on gene expression signatures pertaining to different types of muscle atrophy for the identification of novel key regulatory signals implicated in these degenerative processes. -
Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts Into Bioenergetics
antioxidants Review Biophysical Modulation of the Mitochondrial Metabolism and Redox in Bone Homeostasis and Osteoporosis: How Biophysics Converts into Bioenergetics Feng-Sheng Wang 1,2,†, Re-Wen Wu 3,† , Yu-Shan Chen 1, Jih-Yang Ko 3, Holger Jahr 4,5 and Wei-Shiung Lian 1,2,* 1 Core Laboratory for Phenomics and Diagnostic, Department of Medical Research and Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; [email protected] (F.-S.W.); [email protected] (Y.-S.C.) 2 Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan 3 Department of Orthopedic Surgery, Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; [email protected] (R.-W.W.); [email protected] (J.-Y.K.) 4 Department of Anatomy and Cell Biology, University Hospital RWTH, 52074 Aachen, Germany; [email protected] 5 Department of Orthopedic Surgery, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands * Correspondence: [email protected]; Tel.: +886-7-731-7123 † F.-S.W. and R.-W.W. contribute to this article equally. Abstract: Bone-forming cells build mineralized microstructure and couple with bone-resorbing Citation: Wang, F.-S.; Wu, R.-W.; cells, harmonizing bone mineral acquisition, and remodeling to maintain bone mass homeostasis. Chen, Y.-S.; Ko, J.-Y.; Jahr, H.; Mitochondrial glycolysis and oxidative phosphorylation pathways together with ROS generation Lian, W.-S. Biophysical Modulation of meet the energy requirement for bone-forming cell growth and differentiation, respectively. Moder- the Mitochondrial Metabolism and ate mechanical stimulations, such as weight loading, physical activity, ultrasound, vibration, and Redox in Bone Homeostasis and electromagnetic field stimulation, etc., are advantageous to bone-forming cell activity, promoting Osteoporosis: How Biophysics bone anabolism to compromise osteoporosis development. -
Differential Chromatin Accessibility in Developing Projection Neurons Is Correlated with Transcriptional Regulation of Cell Fate
bioRxiv preprint doi: https://doi.org/10.1101/645572; this version posted May 21, 2019. 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. Differential chromatin accessibility in developing projection neurons is correlated with transcriptional regulation of cell fate Authors: Whitney E. Heavner1,2*, Shaoyi Ji2, James H. Notwell3, Ethan S. Dyer4,5,6, Alex M. Tseng3, Johannes Birgmeier3, Boyoung Yoo3, Gill Bejerano3,7,8,9, Susan K. McConnell2 Affliations: 1Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 2Department of Biology, Stanford University, Stanford, CA 3Department of Computer Science, Stanford University, Stanford, CA 4Stanford Institute for Theoretical Physics, Stanford University, Stanford, CA 5Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 6Google, Mountain View, CA 7Department of Developmental Biology, Stanford University, Stanford, CA 8Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CA 9Department of Biomedical Data Science, Stanford University, Stanford, CA *Correspondence to: W.E.H. ([email protected]) bioRxiv preprint doi: https://doi.org/10.1101/645572; this version posted May 21, 2019. 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. Abstract We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. -
Positive Selection in Transcription Factor Genes
POSITIVE SELECTION IN TRANSCRIPTION FACTOR GENES ALONG THE HUMAN LINEAGE by GABRIELLE CELESTE NICKEL Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Adviser: Dr. Mark D. Adams Department of Genetics CASE WESTERN RESERVE UNIVERSITY January 2009 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Gabrielle Nickel______________________________________________________ candidate for the _Ph.D._______________________________degree *. Helen Salz_______________________________________________ (chair of the committee) Mark Adams______________________________________________ Radhika Atit_______________________________________________ Peter Harte________________________________________________ Joe Nadeau________________________________________________ ________________________________________________ (date) August 28, 2008_______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. 1 TABLE OF CONTENTS Table of Contents……………………………………………………………………………………………………….2 List of Tables……………………………………………………………………………………………………………...6 List of Figures……………………………………………………………………………………………………………..8 List of Abbreviations…………………………………………………………………………………………………10 Glossary………………………………………………………………………………………………..………………….12 Abstract..………………………………………………………………………………………………………………….16 Chapter 1: Introduction and Background………………………………………….……………………...17 Origin of Modern Humans………………………………………………………………………………..19 Human‐chimpanzee