Mapping Cell Type-Specific Transcriptional Enhancers Using High Affinity, 8 Lineage-Specific Ep300 Biochip-Seq 9
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Yildiz et al. Neural Development (2019) 14:5 https://doi.org/10.1186/s13064-019-0129-x RESEARCH ARTICLE Open Access Zebrafish prdm12b acts independently of nkx6.1 repression to promote eng1b expression in the neural tube p1 domain Ozge Yildiz1, Gerald B. Downes2 and Charles G. Sagerström1* Abstract Background: Functioning of the adult nervous system depends on the establishment of neural circuits during embryogenesis. In vertebrates, neurons that make up motor circuits form in distinct domains along the dorsoventral axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear. Methods: We used CRISPR/Cas9 to generate the first germline mutants for prdm12 and employed this resource, together with classical luciferase reporter assays and co-immunoprecipitation experiments, to study prdm12b function in zebrafish. We also generated germline mutants for bhlhe22 and nkx6.1 to examine how these TFs act with prdm12b to control p1 formation. Results: We find that prdm12b mutants lack eng1b expression in the p1 domain and also possess an abnormal touch-evoked escape response. Using luciferase reporter assays, we demonstrate that Prdm12b acts as a transcriptional repressor. We also show that the Bhlhe22 TF binds via the Prdm12b zinc finger domain to form a complex. However, bhlhe22 mutants display normal eng1b expression in the p1 domain. While prdm12 has been proposed to promote p1 fates by repressing expression of the nkx6.1 TF, we do not observe an expansion of the nkx6.1 domain upon loss of prdm12b function, nor is eng1b expression restored upon simultaneous loss of prdm12b and nkx6.1. -
Sexual Dimorphism in the Meiotic Requirement for PRDM9: a Mammalian Evolutionary
bioRxiv preprint doi: https://doi.org/10.1101/2020.03.10.985358; this version posted March 13, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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 1 Sexual dimorphism in the meiotic requirement for PRDM9: a mammalian evolutionary 2 safeguard 3 Short title: 4 Sex-limited requirement of PRDM9 in mice 5 One Sentence Summary: 6 Sex-specific modulation of a meiotic DNA damage checkpoint limits the requirement for PRDM9 in 7 mammalian fertility. 8 9 Authors 10 Natalie R Powers1, Beth L Dumont1, Chihiro Emori1, Raman Akinyanju Lawal1, Catherine Brunton1, Ken 11 Paigen1, Mary Ann Handel1, Ewelina Bolcun-Filas1, Petko M Petkov1, and Tanmoy Bhattacharyya1,* 12 1. The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA. 13 *Correspondence to: [email protected] 14 Abstract: 15 In many mammals, genomic sites for recombination are determined by histone methyltransferase PRMD9. Mice 16 lacking PRDM9 are infertile, but instances of fertility or semi-fertility in the absence of PRDM9 have been 17 reported in mice, canines and a human female. Such findings raise the question of how the loss of PRDM9 is 18 circumvented to maintain reproductive fitness. We show that genetic background and sex-specific modifiers can 19 obviate the requirement for PRDM9 in mice. Specifically, the meiotic DNA damage checkpoint protein CHK2 20 acts as a modifier allowing female-specific fertility in the absence of PRDM9. We also report that in the 21 absence of PRDM9, a PRDM9-independent recombination system is compatible with female meiosis and 22 fertility, suggesting sex-specific regulation of meiotic recombination, a finding with implications for speciation. -
PARRIS WASHINGTON MSNS Candidate
Thesis Defense April 13, 2018; 2:30 PM Distinguishing the Transcriptional Responses Between the Human and Mouse Circadian Clock Resetting Mechanisms PARRIS WASHINGTON MSNS Candidate Under the direction of Jason DeBruyne, Ph.D. Associate Professor, Department of Pharmacology & Toxicology In partial fulfillment of the requirements for the degree Master of Science in Neuroscience F-233_MRC (Building F) Neuroscience Institute Conference Room 720 Westview Drive SW, Atlanta, GA 30310 Graduate Education in Biomedical Sciences Final Examination of PARRIS WASHINGTON For the Degree MASTER OF SCIENCE IN NEUROSCIENCE DISSERTATION COMMITTEE Jason DeBruyne, Ph.D., Research Advisor Department of Pharmacology & Toxicology Morehouse School of Medicine An Zhou, Ph.D. Department of Neurobiology Morehouse School of Medicine Alec Davidson, Ph.D. Department of Neurobiology Morehouse School of Medicine PROFESSOR IN CHARGE OF RESEARCH Jason DeBruyne, Ph.D. Department of Pharmacology & Toxicology Morehouse School of Medicine FIELDS OF STUDY Major Subject: Neuroscience Biomedical Science Presentation I Critical Thinking & Scientific Communication Critical Thinking in Neuroscience Essentials in Neuroscience I Essentials in Neuroscience II Essentials in Neuroscience III Neuroscience Lab Rotation Neuroscience Lab Techniques Research Data Analysis Scientific Integrity Seminar in Biomedical Sciences I Seminar in Biomedical Sciences II Thesis Research Research Focus: Chronobiology, Entrainment, Transcriptional Responses of Human and Mouse Circadian Clock Resetting Mechanisms -
Downloaded from the Gene
bioRxiv preprint doi: https://doi.org/10.1101/2020.07.23.218768; this version posted July 24, 2020. 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. An atlas of lamina-associated chromatin across thirteen human cell types reveals cell-type-specific and multiple subtypes of peripheral heterochromatin a,b c d e Kathleen C. Keough *, Parisha P. Shah*, Nadeera M. Wickramasinghe, Carolyn E. Dundes, e e b e d Angela Chen, Rachel E.A. Salomon, Sean Whalen, Kyle M. Loh, Nicole Dubois, Katherine a,b,f c S. Pollard **, Rajan Jain** a b University of California, San Francisco, CA 94117, USA; Gladstone Institute of Data Science and Biotechnology, c San Francisco, CA 94158, USA; Departments of Medicine and Cell and Developmental Biology, Penn CVI, Perelman d School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Cell, Developmental and e Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Department of Developmental Biology and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, f Stanford, CA 94305 USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA Corresponding authors: Katherine S. Pollard and Rajan Jain Katherine S. Pollard Gladstone Institutes 1650 Owens Street San Francisco, CA 94158 415-732-2711 [email protected] Rajan Jain 09-102 Smilow TRC 3400 Civic Center Blvd Philadelphia, PA 19104 215-573-3011 [email protected] *These authors contributed equally to this work. Running title: (above) Keywords: Lamin-associated domains, peripheral chromatin organization, heterochromatin, chromatin compartmentalization, 3D genome, cellular differentiation and development. -
A Fusion of Pathology in Diabetic Neuropathy MEOX2 Linked With
RESEARCH HIGHLIGHTS NEUROLOGICAL DISORDERS A fusion of pathology in diabetic neuropathy The fusion of proinsulin-expressing bone of factors have been implicated in the the researchers showed that the treatment of marrow cells with neurons could be a process. diabetic rats with insulin led to a reduction in key event in the development of diabetic Chan and colleagues had previously the number of proinsulin-positive cells and neuropathy, according to a recent report found proinsulin- and insulin-positive prevented the prolongation of motor nerve by Lawrence Chan and colleagues. cells — which are normally confined conduction velocity — a sign of neuropathy Diabetic peripheral neuropathy is the to the pancreas — in various organs in — confirming that the appearance of these leading cause of non-traumatic limb mouse and rat models of diabetes, and had cells was due to hyperglycaemia. amputations. The symptoms can be shown that most of these extrapancreatic How the mechanism described by Chan widespread, from numbness, pain and insulin-producing cells originated in the and colleagues relates to several other tingling of the extremities to problems bone marrow. In their latest study, the factors that have been implicated in with the digestive tract, bladder infections researchers discovered that in diabetic diabetic neuropathy, including oxidative and impotence. But the chain of events mice and rats with neuropathy, bone- stress and growth factor deficiency, that leads to nerve damage in diabetes is marrow-derived cells that expressed remains an open question. not well described, and current treatments proinsulin fused with neurons in the Rebecca Craven are designed to relieve discomfort and sciatic nerve and dorsal root ganglion, References and links prevent further tissue damage. -
ES-62 Suppression of Arthritis Reflects Epigenetic Rewiring of Synovial Fibroblasts to a Joint-Protective Phenotype
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.08.331942; this version posted October 8, 2020. 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. ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype Marlene Corbet1, Miguel A Pineda1, Kun Yang1, Anuradha Tarafdar1, Sarah McGrath1, Rinako Nakagawa2, Felicity E Lumb3, William Harnett3* and Margaret M Harnett1* 1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 2Immunity and Cancer, Francis Crick Institute, London NW1 1AT, UK 3Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK * Joint corresponding authors: [email protected] (MMH), [email protected] (WH) Short title: ES-62 rewires synovial fibroblasts to a resolving phenotype 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.08.331942; this version posted October 8, 2020. 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 The parasitic worm product, ES-62 protects against collagen-induced arthritis, a mouse model of rheumatoid arthritis (RA) by suppressing the synovial fibroblast (SF) responses perpetuating inflammation and driving joint destruction. Such SF responses are shaped during disease progression by the inflammatory microenvironment of the joint that promotes remodelling of their epigenetic landscape, inducing an “aggressive” pathogenic SF phenotype. Critically, exposure to ES-62 in vivo induces a stably imprinted “safe” phenotype that exhibits responses more typical of healthy SFs. -
In Vivo Binding of PRDM9 Reveals Interactions with Noncanonical Genomic Sites C Grey, Ja Clement, J Buard, B Leblanc, I Gut, M Gut, L
In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites C Grey, Ja Clement, J Buard, B Leblanc, I Gut, M Gut, L. Duret, B de Massy To cite this version: C Grey, Ja Clement, J Buard, B Leblanc, I Gut, et al.. In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites. Genome Research, Cold Spring Harbor Laboratory Press, 2017, 27 (4), pp.580-590. 10.1101/gr.217240.116. hal-01505240 HAL Id: hal-01505240 https://hal.archives-ouvertes.fr/hal-01505240 Submitted on 10 Jun 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Downloaded from genome.cshlp.org on June 10, 2021 - Published by Cold Spring Harbor Laboratory Press Research In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites Corinne Grey,1,6 Julie A.J. Clément,1,6 Jérôme Buard,1 Benjamin Leblanc,2 Ivo Gut,3,4 Marta Gut,3,4 Laurent Duret,5 and Bernard de Massy1 1Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 34396 Montpellier Cedex -
Lack of Rybp in Mouse Embryonic Stem Cells Impairs Cardiac Differentiation O
Page 1 of 43 1 Lack of Rybp in Mouse Embryonic Stem Cells Impairs Cardiac Differentiation O. Ujhelly1, V. Szabo2, G. Kovacs2, F. Vajda2, S. Mallok4, J. Prorok5, K. Acsai6, Z. Hegedus3, S. Krebs4, A. Dinnyes1,7 and M. K. Pirity2 * 1 BioTalentum Ltd, H-2100 Gödöllö, Hungary 2 Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, H-6726 Szeged, Hungary 3 Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, H-6726 Szeged, Hungary 4 Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany 5 Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary 6 MTA-SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary 7 Molecular Animal Biotechnology Laboratory, Szent Istvan University, Gödöllö, Hungary * Author for correspondence at Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, H-6726 Szeged, Hungary Stem Cells and Development Ring1 and Yy1 Binding Protein (Rybp) has been implicated in transcriptional regulation, apoptotic signaling and as a member of the polycomb repressive complex 1 has important function in regulating pluripotency and differentiation of embryonic stem cells. Earlier, we have proven that Rybp plays essential role in mouse embryonic and central nervous system development. This work identifies Rybp, as a critical regulator of heart development. Rybp is readily detectable in the developing mouse heart from day 8.5 of embryonic development. Prominent Rybp expression persists during all embryonic stages and Rybp marks differentiated cell types of the heart. By utilizing rybp null embryonic stem cells (ESCs) in an in vitro cardiac Lack of Rybp in Mouse Embryonic Stem Cells Impairs Cardiac Differentiation (doi: 10.1089/scd.2014.0569) differentiation assay we found that rybp null ESCs do not form rhythmically beating cardiomyocytes. -
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 -
Comprehensive Epigenome Characterization Reveals Diverse Transcriptional Regulation Across Human Vascular Endothelial Cells
Nakato et al. Epigenetics & Chromatin (2019) 12:77 https://doi.org/10.1186/s13072-019-0319-0 Epigenetics & Chromatin RESEARCH Open Access Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells Ryuichiro Nakato1,2† , Youichiro Wada2,3*†, Ryo Nakaki4, Genta Nagae2,4, Yuki Katou5, Shuichi Tsutsumi4, Natsu Nakajima1, Hiroshi Fukuhara6, Atsushi Iguchi7, Takahide Kohro8, Yasuharu Kanki2,3, Yutaka Saito2,9,10, Mika Kobayashi3, Akashi Izumi‑Taguchi3, Naoki Osato2,4, Kenji Tatsuno4, Asuka Kamio4, Yoko Hayashi‑Takanaka2,11, Hiromi Wada3,12, Shinzo Ohta12, Masanori Aikawa13, Hiroyuki Nakajima7, Masaki Nakamura6, Rebecca C. McGee14, Kyle W. Heppner14, Tatsuo Kawakatsu15, Michiru Genno15, Hiroshi Yanase15, Haruki Kume6, Takaaki Senbonmatsu16, Yukio Homma6, Shigeyuki Nishimura16, Toutai Mitsuyama2,9, Hiroyuki Aburatani2,4, Hiroshi Kimura2,11,17* and Katsuhiko Shirahige2,5* Abstract Background: Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phe‑ notypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from diferent organs are not well understood. Results: To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome‑wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We developed a robust procedure for comparative epigenome analysis that circumvents variations at the level of the individual and technical noise derived from sample preparation under various conditions. Through this approach, we identifed 3765 EC‑specifc enhancers, some of which were associated with disease‑associated genetic variations. -
Saethre–Chotzen Syndrome Caused by TWIST 1 Gene Mutations: Functional Differentiation from Muenke Coronal Synostosis Syndrome
European Journal of Human Genetics (2006) 14, 39–48 & 2006 Nature Publishing Group All rights reserved 1018-4813/06 $30.00 www.nature.com/ejhg ARTICLE Saethre–Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome Wolfram Kress*,1, Christian Schropp2, Gabriele Lieb2, Birgit Petersen2, Maria Bu¨sse-Ratzka2, Ju¨rgen Kunz3, Edeltraut Reinhart4, Wolf-Dieter Scha¨fer5, Johanna Sold5, Florian Hoppe6, Jan Pahnke6, Andreas Trusen7, Niels So¨rensen8,Ju¨rgen Krauss8 and Hartmut Collmann8 1Institute of Human Genetics, University of Wu¨rzburg, Wu¨rzburg, Germany; 2Department of Pediatrics, University of Wu¨rzburg, Wu¨rzburg, Germany; 3Institute of Human Genetics, University of Marburg, Marburg, Germany; 4Department of Maxillo-facial Surgery, University of Wu¨rzburg, Wu¨rzburg, Germany; 5Department of Ophthalmology, University of Wu¨rzburg, Wu¨rzburg, Germany; 6Department of Otorhinolaryngology, University of Wu¨rzburg, Wu¨rzburg, Germany; 7Department of Diagnostic Radiology, University of Wu¨rzburg, Wu¨rzburg, Germany; 8Sect. Pediatric Neurosurgery, University of Wu¨rzburg, Wu¨rzburg, Germany The Saethre–Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke’s syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3. Within a total of 124 independent pedigrees, 39 (71 patients) were identified to carry 25 different mutations of TWIST 1 including 14 novel mutations, to which six whole gene deletions were added. -
GLI1 Transcription Axis Involved in Cancer Drug Resistance, Overall Survival and Therapy Prognosis in Lung Cancer Patients
www.impactjournals.com/oncotarget/ Oncotarget, Advance Publications 2017 Epigenomic study identifies a novel mesenchyme homeobox2- GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients Armas López Leonel1, Piña-Sánchez Patricia2, Arrieta Oscar3, Guzman de Alba Enrique4, Ortiz Quintero Blanca4, Santillán Doherty Patricio4, Christiani David C.5, Zúñiga Joaquín4 and Ávila-Moreno Federico1,4 1National University Autonomous of México (UNAM), Facultad de Estudios Superiores (FES) Iztacala, Biomedicine Research Unit (UBIMED), Lung Diseases And Cancer Epigenomics Laboratory, Mexico State, Mexico 2Instituto Mexicano del Seguro Social (IMSS), Centro Medico Nacional (CMN) Siglo XXI, Unidad de Investigación Médica en Enfermedades Oncológicas (UIMEO), Molecular Oncology Laboratory, Mexico City, Mexico 3National Cancer Institute (INCAN), Thoracic Oncology Clinic, Mexico City, Mexico 4National Institute of Respiratory Diseases (INER), Ismael Cosío Villegas, Mexico City, Mexico 5Harvard Medical School, Harvard School of Public Health, Department of Environmental Health, Boston Massachusetts, USA Correspondence to: Federico Ávila Moreno, email: [email protected], [email protected] Keywords: lung cancer, homeobox transcription factors, Epigenetics cancer drug resistance, overall survival, treatment prognosis Received: May 26, 2016 Accepted: April 11, 2017 Published: May 09, 2017 Copyright: Leonel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated.