DOCSLIB.ORG

Role of the Nuclear Receptor Rev-Erb Alpha in Circadian Food Anticipation and Metabolism Julien Delezie

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of the Nuclear Receptor Rev-Erb Alpha in Circadian Food Anticipation and Metabolism Julien Delezie Role of the nuclear receptor Rev-erb alpha in circadian food anticipation and metabolism Julien Delezie To cite this version: Julien Delezie. Role of the nuclear receptor Rev-erb alpha in circadian food anticipation and metabolism. Neurobiology. Université de Strasbourg, 2012. English. NNT : 2012STRAJ018. tel- 00801656 HAL Id: tel-00801656 https://tel.archives-ouvertes.fr/tel-00801656 Submitted on 10 Apr 2013 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. UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTE CNRS UPR 3212 · Institut des Neurosciences Cellulaires et Intégratives THÈSE présentée par : Julien DELEZIE soutenue le : 29 juin 2012 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline/ Spécialité : Neurosciences Rôle du récepteur nucléaire Rev-erbα dans les mécanismes d’anticipation des repas et le métabolisme THÈSE dirigée par : M CHALLET Etienne Directeur de recherche, université de Strasbourg RAPPORTEURS : M PFRIEGER Frank Directeur de recherche, université de Strasbourg M KALSBEEK Andries Professeur, université d’Amsterdam M ALBRECHT Urs Professeur, université de Fribourg THÈSE présentée à la Faculté des Sciences de la Vie et de la Santé de l’Université de Strasbourg pour l’obtention du grade de Docteur Spécialité : Neurosciences par Julien Delezie Role of the nuclear receptor Rev-erbα in circadian food anticipation and metabolism Rôle du récepteur nucléaire Rev-erbα dans les mécanismes d’anticipation des repas et le métabolisme Soutenue le 29 juin 2012 Membres du jury Directeur de thèse Dr Etienne Challet (Strasbourg, France) Rapporteur interne Dr Frank Pfrieger (Strasbourg, France) Rapporteur externe Prof Urs Albrecht (Fribourg, Switzerland) Rapporteur externe Prof Andries Kalsbeek (Amsterdam, Netherlands) 1 2 A vous deux, 3 4 « Le Soleil envie la Terre comme la Terre envie le Soleil. L’un reçoit la lumière et l’autre brille de mille feux. » J.D. 5 6 Note to the reader The work presented in this manuscript was carried out from 2008 to 2012 in the: - Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, University of Strasbourg, Strasbourg, France; and in collaboration with other laboratories: - Department of Ecology, Physiology, and Ethology, Hubert Curien Multidisciplinary Institute, University of Strasbourg, Strasbourg, France (short stay of three months); - Valrose Institute of Biology, University of Nice, Nice, France (short stay of two months); - Physiology of Reproduction and Behavior, François Rabelais University, French Institute of the Horse and Equitation, Nouzilly, France. Parts of this PhD thesis have been published in peer-reviewed journals: Delezie J, Dumont S, Dardente H, Oudart H, Grechez A, Klosen P, Teboul M, Delaunay F, Pevet P and Challet E. The nuclear receptor REV-ERBα is required for the circadian balance of carbohydrate and lipid metabolism. FASEB Journal. 2012; 26(8): 3321-35. Delezie J, Challet E. Interactions between metabolism and circadian clocks: reciprocal disturbances. Ann N Y Acad Sci. 2011;1243(1):30-46. (Review) and in general-public journals: Delezie J, Pevet P, Challet E. Quand notre santé métabolique dépend de nos horloges internes : Implications du gène d’horloge Rev-erbα dans l’obésité. Médecine/sciences 2012 August-September. 8-9, vol. 28. (French review) Delezie J, Challet E. La rythmicité circadienne au cœur du métabolisme. Biofutur 2011, 325, 31-34. (French review) Challet E, Delezie J, Mendoza J. Circadian clocks and nutrition. Correspondances en Métabolisme Hormones, Diabètes et Nutrition 2009 May- June, Vol. XIII. N°3. (French review) 7 8 Acknowledgments/Remerciements A few words in Shakespeare’s language… I am deeply grateful to the members of my thesis committee, Andries Kalsbeek, Franck Pfrieger and Urs Albrecht, for having accepted to evaluate this work. Et un peu plus dans la langue de Voltaire… J’exprime toute ma reconnaissance à l’égard de mon directeur de thèse, Etienne Challet, pour m’avoir accueilli au sein de son équipe, encadré et soutenu pendant plus de trois années. J’ai énormément appris à tes côtés en pouvant notamment profiter de ton excellente culture en chronobiologie. Tu m’as donné beaucoup de liberté dans mon travail tout en sachant être présent quand il le fallait – et ce, même dans les moments les plus ardus. Je tiens à remercier Jorge Mendoza, qui m’a pris comme stagiaire dès mes études en Master et qui m’a aidé tout au long de ces années. Tu m’as transmis le goût de l’effort. Sur les plans scientifique et technique, j’ai beaucoup appris avec toi. Ma gratitude s’adresse également à Stéphanie Dumont. A tes côtés, j’ai profité d’une formation exceptionnelle sur le plan technique et d’une aide précieuse au quotidien. Sans toi, une partie de cette thèse n’aurait jamais vu le jour. Un grand merci à Sylviane Gourmelen qui m’a souvent assisté dans le suivi des animaux durant cette thèse. Tu as toujours été spontanée et avenante. Mes remerciements se destinent également à Franck Delaunay, Hugues Dardente et Hugues Oudart. Avec de grandes qualités pédagogiques, vous m’avez chacun instruit sur différents domaines scientifiques qui m’étaient jusqu’alors quasi inconnus – je pense en particulier au métabolisme ou à la génétique. Merci pour le temps que vous avez consacré à nos recherches. 9 Je pense aussi à André Malan. J’aurais souhaité apprendre davantage avec vous, merci pour les quelques bribes de connaissance que vous m’avez transmises en statistiques notamment. Je suis reconnaissant envers Sophie Reibel et Laurence Huck, pour leur aide inestimable dans la gestion des animaux en transgénique. Je pense de même aux autres personnes de l’animalerie, en particulier Anita Wulgué. Merci à Sophie Brangolo et Aline Grechez-Cassiau de m’avoir formé à l’étude des hépatocytes et aidé durant mes séjours à Nice, j’ai particulièrement apprécié votre compagnie. Merci également à Michèle Teboul de m’avoir assisté dans mes premiers pas en biologie moléculaire. Je remercie aussi les personnes du labo qui m’ont aidé : Cristina Sandu, pour ta précieuse aide en biologie moléculaire ; Dominique Ciocca, pour le temps que tu as consacré à nos expériences notamment en actimétrie ; Paul Klosen, pour tes nombreuses réponses à mes questions scientifiques ; Marie-Paule Felder, pour nos discussions et tes conseils en génétique ; David Hicks, pour avoir pris le soin de relire et corriger quelques parties délicates de ma thèse – où il convient de l’écrire, le style Proustien dans mes écrits anglais bruts était quelque peu indigeste. Je tiens également à remercier vivement Mireille Masson-Pévet et Paul Pévet pour leur soutien ; ainsi que Virginie Laurent-Gydé, Daniel Clesse, Dominique Streicher et Jean-George Lorentz, pour leur sympathie. Merci à toutes les stagiaires qui sont passées dans l’équipe, en particulier Magaly, Marion et Antonia, pour leur aide dans diverses expériences. Je ne saurais terminer cette partie de remerciements sans avoir quelques mots pour les post-doctorants, doctorants, pré-doctorants avec qui j’ai partagé d’excellents moments : Coralie, Cathy, Jevita, Slava, Edith, Stefanie, Ouafa, Tounès, Cristina, Mio, Marie-Audrey, Rajae, Domitille, Daniela, Lucas, Laurent, Adrien, Alexis, Julien, Vy, David, Madah, Taole… bon courage à tous pour la suite de vos études, pour ce que vous déciderez d’entreprendre. (Au passage : Coralie, Cathy, Edith, Cristina (Sandu), Ouafa, Rajae, Julien, Vy, ainsi qu’Adrien (l’intrus géochimiste), merci encore pour ce final d’une grande saveur.) 10 De façon plus particulière, j’aimerais remercier des personnes qui ont influencé mon parcours scolaire et universitaire : Mme Hen, mon professeur de Biologie et Nutrition en BEP Carrières Sanitaires et Sociales, pour avoir un jour prononcé quelques mots qui ont eu une portée singulière et qui font encore écho en moi aujourd’hui ; Mme Max, mon professeur de Biologie lorsque j’entreprenais des études en Sciences Médico-Sociales, pour m’avoir donné goût à la biologie, peut- être sans le savoir ; Mme Weber, professeur de Français, pour m’avoir mis plusieurs livres entre les mains dont le surprenant Candide, qui a depuis délivré tout son sens ; et M Dalle Mese, professeur de Philosophie, pour m’avoir évalué comme un littéraire et fait comprendre que derrière les mots se cache souvent une imposture. J’ai également une pensée chaleureuse pour mes (lointains) amis de « Psycho » : Amandine, Alexandra, Pierre – la communauté. Nous avons partagé quelques années ensemble ; vous m’avez chacun marqué par vos personnalités, par nos échanges, par votre bienveillance. « Et c'est à cet endroit […] » que je tiens également à t’ajouter. J’ai beaucoup écrit par le passé, tu m’as toujours lu avec un rare discernement. Merci Ewa. Sans oublier Guillaume et Jérémy qui m’ont aussi inspiré. Les détours de la vie ne nous ont pas épargné, nous avons su cependant nous retrouver aux croisements de différents chemins, sans que le temps n’affecte nos amitiés. Mes derniers mots s’adressent à « mon cœur ma mie mon âme », Caroline. Alors peut-être
Load more

Recommended publications
  • The Ins and Outs of Circadian Timekeeping Steven a Brown* and Ueli Schibler†
    gd9507.qxd 11/10/1999 12:14 PM Page 588 588 The ins and outs of circadian timekeeping Steven A Brown* and Ueli Schibler† Recent research in Drosophila and in mammals has generated The mechanism by which light signals entrain the clock is fascinating new models for how circadian clocks in these another topic of intense interest, and will be our other focus. organisms are reset by light and how these clocks, in turn, direct circadian outputs. Though light perception by the central clock is Central clock mechanisms: a brief summary ocular in mammals, it probably proceeds via a mechanism In all cases examined to date, circadian clocks have been separate from traditional visual transduction. In Drosophila, one cell-autonomous: a single cell can generate and maintain mechanism is non-ocular and is in fact present in many different self-sustained circadian oscillations. The molecular basis tissues. In both organisms, the cryptochrome family of for these rhythms may rely on a negative feedback loop in photoreceptor-like molecules plays a role in the circadian clock, which clock proteins negatively regulate their own abun- though their function is incompletely understood. Moreover, dance or activity. This regulation may occur both at the although a master clock resides in the brain, a functional clock transcriptional and at the post-transcriptional level. For appears to reside in most cells of the body. In these tissues, at example, in the bread mold Neurospora crassa, the Fre- least some output genes are controlled at the transcriptional quency protein negatively regulates its own transcription level directly by clock proteins; others appear to be regulated by by interfering with the ability of the White-collar-1 and cascades of circadian transcription factors.
    [Show full text]
  • Distinct Patterns of Period Gene Expression in the Suprachiasmatic Nucleus Underlie Circadian Clock Photoentrainment by Advances Or Delays
    University of Massachusetts Medical School eScholarship@UMMS Neurobiology Publications and Presentations Neurobiology 2011-10-11 Distinct patterns of Period gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays William J. Schwartz University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/neurobiology_pp Part of the Neuroscience and Neurobiology Commons Repository Citation Schwartz WJ, Tavakoli-Nezhad M, Lambert CM, Weaver DR, de la Iglesia HO. (2011). Distinct patterns of Period gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays. Neurobiology Publications and Presentations. https://doi.org/10.1073/ pnas.1107848108. Retrieved from https://escholarship.umassmed.edu/neurobiology_pp/114 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Neurobiology Publications and Presentations by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Distinct patterns of Period gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays William J. Schwartza,1, Mahboubeh Tavakoli-Nezhada, Christopher M. Lambertb, David R. Weaverb, and Horacio O. de la Iglesiac,1 Departments of aNeurology and bNeurobiology, University of Massachusetts Medical School, Worcester, MA 01655; and cDepartment of Biology, University of Washington, Seattle, WA 98195 Edited by Michael Rosbash, Howard Hughes Medical Institute, Waltham, MA, and approved September 9, 2011 (received for review May 19, 2011) The circadian clock in the mammalian hypothalamic suprachias- and Per3) genes is activated. PER proteins accumulate in the matic nucleus (SCN) is entrained by the ambient light/dark cycle, cytoplasm, are regulated through their phosphorylation and their which differentially acts to cause the clock to advance or delay.
    [Show full text]
  • SHARP1 (BHLHE41) Mouse Monoclonal Antibody [Clone ID: OTI3H4] Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA806354 SHARP1 (BHLHE41) Mouse Monoclonal Antibody [Clone ID: OTI3H4] Product data: Product Type: Primary Antibodies Clone Name: OTI3H4 Applications: IHC, WB Recommended Dilution: WB 1:2000, IHC 1:150 Reactivity: Human Host: Mouse Isotype: IgG1 Clonality: Monoclonal Immunogen: Human recombinant protein fragment corresponding to amino acids 1-297 of human BHLHE41(NP_110389) produced in E.coli. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 50.3 kDa Gene Name: basic helix-loop-helix family member e41 Database Link: NP_110389 Entrez Gene 79365 Human Q9C0J9 Background: This gene encodes a basic helix-loop-helix protein expressed in various tissues. The encoded protein can interact with ARNTL or compete for E-box binding sites in the promoter of PER1 and repress CLOCK/ARNTL's transactivation of PER1. This gene is believed to be involved in the control of circadian rhythm and cell differentiation. Defects in this gene are associated with the short sleep phenotype. [provided by RefSeq, Feb 2014] This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 SHARP1 (BHLHE41) Mouse Monoclonal Antibody [Clone ID: OTI3H4] – TA806354 Synonyms: BHLHB3; DEC2; hDEC2; SHARP1 Protein Families: Transcription Factors Protein Pathways: Circadian rhythm - mammal Product images: HEK293T cells were transfected with the pCMV6- ENTRY control (Left lane) or pCMV6-ENTRY BHLHE41 ([RC206882], Right lane) cDNA for 48 hrs and lysed.
    [Show full text]
  • Core Transcriptional Regulatory Circuitries in Cancer
    Oncogene (2020) 39:6633–6646 https://doi.org/10.1038/s41388-020-01459-w REVIEW ARTICLE Core transcriptional regulatory circuitries in cancer 1 1,2,3 1 2 1,4,5 Ye Chen ● Liang Xu ● Ruby Yu-Tong Lin ● Markus Müschen ● H. Phillip Koeffler Received: 14 June 2020 / Revised: 30 August 2020 / Accepted: 4 September 2020 / Published online: 17 September 2020 © The Author(s) 2020. This article is published with open access Abstract Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type- specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC). Here, we summarize recent progress in computational reconstitution and biologic exploration of CRCs across various human malignancies, and consolidate the strategy and methodology for CRC discovery. We also discuss the genetic basis and therapeutic vulnerability of CRC, and highlight new frontiers and future efforts for the study of CRC in cancer. Knowledge of CRC in cancer is fundamental to understanding cancer-specific transcriptional addiction, and should provide important insight to both pathobiology and therapeutics. 1234567890();,: 1234567890();,: Introduction genes. Till now, one critical goal in biology remains to understand the composition and hierarchy of transcriptional Transcriptional regulation is one of the fundamental mole- regulatory network in each specified cell type/lineage.
    [Show full text]
  • 2009 Riboclub Program
    RiboClub 2017 in association with the Swiss National Center of Competence in RNA & Disease. September 24-28 RNPs: the Good, the Bad and the Ugly Insights into RNA-protein complex assembly and function in health and disease Hotel et Villégiature Chéribourg 2603 Chemin du Parc Orford (Magog) Quebec, Canada Sunday, September 24th 15:00 – 18:00 Registration for early arrivals 18:00 – 19:30 Welcome reception 19:30 – 21:30 Opening dinner Monday, September 25th 08:00 – 08:45 Registration 08:45 – 08:55 Opening Notes and Announcements (Sherif Abou Elela) 08:55 – 09:10 Welcome Notes by Beat Nobs, Ph.D., Swiss Ambassador to Canada 09:10 – 09:15 Presentation of Keynote speaker (Oliver Mühlemann) 09:15 – 10:15 Keynote presentation From bench to clinical trial: microRNA 122 as an antiviral target for hepatitis C virus Peter Sarnow, Stanford University, Stanford 10:15 – 10:45 Coffee break Session 1: Non-coding RNA function Chair: Martin Jinek (Host: Benoit Chabot) 10:45 – 10:50 Introduction by Martin Jinek 10:50 – 11:05 Mbnl1-dependent mis-regulation and mis-splicing of a conserved myogenic lncRNA in myotonic dystrophy type 1 Pascal Chartrand, Universite de Montreal, Montreal 11:05 – 11:30 Non-canonical function of DGCR8 controls mESCs exit from pluripotency Constance Ciaudo, ETH Zurich, Zurich 11:30 – 11:45 microRNAs use different ways to regulate gene expression in animals Martin Simard, Universite Laval, Quebec 11:45 – 12:10 Structure, evolution and targeting of non coding RNAs Gabriele Varani, University of Washington, Seattle 12:10 – 12:35 Structural
    [Show full text]
  • Dermo-1: a Novel Twist-Related Bhlh Protein Expressed in The
    DEVELOPMENTAL BIOLOGY 172, 280±292 (1995) Dermo-1: A Novel Twist-Related bHLH Protein View metadata,Expressed citation and similar in papers the at core.ac.uk Developing Dermis brought to you by CORE provided by Elsevier - Publisher Connector Li Li, Peter Cserjesi,1 and Eric N. Olson2 Department of Biochemistry and Molecular Biology, Box 117, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 Transcription factors belonging to the basic helix±loop±helix (bHLH) family have been shown to control differentiation of a variety of cell types. Tissue-speci®c bHLH proteins dimerize preferentially with ubiquitous bHLH proteins to form heterodimers that bind the E-box consensus sequence (CANNTG) in the control regions of target genes. Using the yeast two-hybrid system to screen for tissue-speci®c bHLH proteins, which dimerize with the ubiquitous bHLH protein E12, we cloned a novel bHLH protein, named Dermo-1. Within its bHLH region, Dermo-1 shares extensive homology with members of the twist family of bHLH proteins, which are expressed in embryonic mesoderm. During mouse embryogenesis, Dermo- 1 showed an expression pattern similar to, but distinct from, that of mouse twist. Dermo-1 was expressed at a low level in the sclerotome and dermatome of the somites, and in the limb buds at Day 10.5 post coitum (p.c.), and accumulated predominantly in the dermatome, prevertebrae, and the derivatives of the branchial arches by Day 13.5 p.c. As differentiation of prechondrial cells proceeded, Dermo-1 expression became restricted to the perichondrium. Expression of Dermo-1 increased continuously in the dermis through Day 17.5 p.c.
    [Show full text]
  • The Title of the Dissertation
    UNIVERSITY OF CALIFORNIA SAN DIEGO Novel network-based integrated analyses of multi-omics data reveal new insights into CD8+ T cell differentiation and mouse embryogenesis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics and Systems Biology by Kai Zhang Committee in charge: Professor Wei Wang, Chair Professor Pavel Arkadjevich Pevzner, Co-Chair Professor Vineet Bafna Professor Cornelis Murre Professor Bing Ren 2018 Copyright Kai Zhang, 2018 All rights reserved. The dissertation of Kai Zhang is approved, and it is accept- able in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California San Diego 2018 iii EPIGRAPH The only true wisdom is in knowing you know nothing. —Socrates iv TABLE OF CONTENTS Signature Page ....................................... iii Epigraph ........................................... iv Table of Contents ...................................... v List of Figures ........................................ viii List of Tables ........................................ ix Acknowledgements ..................................... x Vita ............................................. xi Abstract of the Dissertation ................................. xii Chapter 1 General introduction ............................ 1 1.1 The applications of graph theory in bioinformatics ......... 1 1.2 Leveraging graphs to conduct integrated analyses .......... 4 1.3 References .............................. 6 Chapter 2 Systematic
    [Show full text]
  • Regulation of Drosophila Circadian Rhythms by Mirna Let-7 Is Mediated by a Regulatory Cycle
    ARTICLE Received 10 Jul 2014 | Accepted 10 Oct 2014 | Published 24 Nov 2014 DOI: 10.1038/ncomms6549 Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle Wenfeng Chen1,*, Zhenxing Liu1,*, Tianjiao Li1, Ruifeng Zhang1, Yongbo Xue1, Yang Zhong1, Weiwei Bai1, Dasen Zhou1 & Zhangwu Zhao1 MicroRNA-mediated post-transcriptional regulations are increasingly recognized as important components of the circadian rhythm. Here we identify microRNA let-7, part of the Drosophila let-7-Complex, as a regulator of circadian rhythms mediated by a circadian regulatory cycle. Overexpression of let-7 in clock neurons lengthens circadian period and its deletion attenuates the morning activity peak as well as molecular oscillation. Let-7 regulates the circadian rhythm via repression of CLOCKWORK ORANGE (CWO). Conversely, upregulated cwo in cwo-expressing cells can rescue the phenotype of let-7-Complex overexpression. Moreover, circadian prothoracicotropic hormone (PTTH) and CLOCK- regulated 20-OH ecdysteroid signalling contribute to the circadian expression of let-7 through the 20-OH ecdysteroid receptor. Thus, we find a regulatory cycle involving PTTH, a direct target of CLOCK, and PTTH-driven miRNA let-7. 1 Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China. * These authors contributed equally to this work. Correspondence and requests for materials should be addressed to Z.Z. (email: [email protected]). NATURE COMMUNICATIONS | 5:5549 | DOI: 10.1038/ncomms6549 | www.nature.com/naturecommunications 1 & 2014 Macmillan Publishers Limited. All rights reserved. ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/ncomms6549 lmost all animals display a wide range of circadian bantam-dependent regulation of Clk expression is required for rhythms in behaviour and physiology, such as locomotor circadian rhythm.
    [Show full text]
  • A Circadian Biomarker Associated with Breast Cancer in Young Women
    268 Cancer Epidemiology, Biomarkers & Prevention Period3 Structural Variation: A Circadian Biomarker Associated with Breast Cancer in Young Women Yong Zhu,1 Heather N. Brown,1 Yawei Zhang,1 Richard G. Stevens,2 and Tongzhang Zheng1 1Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut and 2University of Connecticut Health Center, Farmington, Connecticut Abstract Circadian disruption has been indicated as a risk factor for blood samples collected from a recently completed breast breast cancer in recent epidemiologic studies. A novel cancer case-control study in Connecticut. There were 389 finding in circadian biology is that genes responsible for Caucasian cases and 432 Caucasian controls included in our circadian rhythm also regulate many other biological path- analysis. We found that the variant Per3 genotype (heterozy- ways, including cell proliferation, cell cycle regulation, and gous + homozygous 5-repeat alleles) was associated with an apoptosis. Therefore, mutations in circadian genes could increased risk of breast cancer among premenopausal women conceivably result in deregulation of these processes and (odds ratio, 1.7; 95% confidence interval, 1.0-3.0). Our find- contribute to tumor development, and be markers for ing suggests that the circadian genes might be a novel panel susceptibility to human cancer. In this study, we investi- of potential biomarkers for breast cancer and worth further gated the association between an exonic length variation in a investigation. (Cancer Epidemiol Biomarkers Prev circadian gene, Period3 (Per3), and breast cancer risk using 2005;14(1):268–70) Introduction Genetic determinants have been found to be responsible for a Per2 gene can activate c-Myc signaling pathways leading to fundamental biological phenomenon: a universal 24-hour genomic instability and cell proliferation.
    [Show full text]
  • NPAS2 As a Transcriptional Regulator of Non-Rapid Eye Movement Sleep: Genotype and Sex Interactions
    NPAS2 as a transcriptional regulator of non-rapid eye movement sleep: Genotype and sex interactions Paul Franken*†‡, Carol A. Dudley§, Sandi Jo Estill§, Monique Barakat*, Ryan Thomason¶, Bruce F. O’Hara¶, and Steven L. McKnight‡§ §Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390; *Department of Biological Sciences, Stanford University, Stanford, CA 94305; ¶Department of Biology, University of Kentucky, Lexington, KY 40506; and †Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne-Dorigny, Switzerland Contributed by Steven L. McKnight, March 13, 2006 Because the transcription factor neuronal Per-Arnt-Sim-type sig- delta frequency range is a sensitive marker of time spent awake (4, nal-sensor protein-domain protein 2 (NPAS2) acts both as a sensor 7) and local cortical activation (8) and is therefore widely used as and an effector of intracellular energy balance, and because sleep an index of NREMS need and intensity. is thought to correct an energy imbalance incurred during waking, The PAS-domain proteins, CLOCK, BMAL1, PERIOD-1 we examined NPAS2’s role in sleep homeostasis using npas2 (PER1), and PER2, play crucial roles in circadian rhythm gener- knockout (npas2؊/؊) mice. We found that, under conditions of ation (9). The NPAS2 paralog CLOCK, like NPAS2, can induce the increased sleep need, i.e., at the end of the active period or after transcription of per1, per2, cryptochrome-1 (cry1), and cry2. PER and sleep deprivation (SD), NPAS2 allows for sleep to occur at times CRY proteins, in turn, inhibit CLOCK- and NPAS2-induced when mice are normally awake. Lack of npas2 affected electroen- transcription, thereby closing a negative-feedback loop that is cephalogram activity of thalamocortical origin; during non-rapid thought to underlie circadian rhythm generation.
    [Show full text]
  • The for Report 07-08
    THE CENTER FOR INTEGRATIVE GENOMICS REPORT 07-08 www.unil.ch/cig Table of Contents INTRODUCTION 2 The CIG at a glance 2 The CIG Scientific Advisory Committee 3 Message from the Director 4 RESEARCH 6 Richard Benton Chemosensory perception in Drosophila: from genes to behaviour 8 Béatrice Desvergne Networking activity of PPARs during development and in adult metabolic homeostasis 10 Christian Fankhauser The effects of light on plant growth and development 12 Paul Franken Genetics and energetics of sleep homeostasis and circadian rhythms 14 Nouria Hernandez Mechanisms of basal and regulated RNA polymerase II and III transcription of ncRNA in mammalian cells 16 Winship Herr Regulation of cell proliferation 18 Henrik Kaessmann Mammalian evolutionary genomics 20 Sophie Martin Molecular mechanisms of cell polarization 22 Liliane Michalik Transcriptional control of tissue repair and angiogenesis 24 Alexandre Reymond Genome structure and expression 26 Andrzej Stasiak Functional transitions of DNA structure 28 Mehdi Tafti Genetics of sleep and the sleep EEG 30 Bernard Thorens Molecular and physiological analysis of energy homeostasis in health and disease 32 Walter Wahli The multifaceted roles of PPARs 34 Other groups at the Génopode 37 CORE FACILITIES 40 Lausanne DNA Array Facility (DAFL) 42 Protein Analysis Facility (PAF) 44 Core facilities associated with the CIG 46 EDUCATION 48 Courses and lectures given by CIG members 50 Doing a PhD at the CIG 52 Seminars and symposia 54 The CIG annual retreat 62 The CIG and the public 63 Artist in residence at the CIG 63 PEOPLE 64 1 Introduction The Center for IntegratiVE Genomics (CIG) at A glance The Center for Integrative Genomics (CIG) is the newest depart- ment of the Faculty of Biology and Medicine of the University of Lausanne (UNIL).
    [Show full text]
  • P53 Regulates Myogenesis by Triggering the Differentiation
    CORE Metadata, citation and similar papers at core.ac.uk Provided by PubMed Central p53 Regulates Myogenesis by Triggering the Differentiation Activity of pRb Alessandro Porrello, Maria Antonietta Cerone, Sabrina Coen, Aymone Gurtner, Giulia Fontemaggi, Letizia Cimino, Giulia Piaggio, Ada Sacchi, and Silvia Soddu Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Center for Experimental Research, 00158 Rome, Italy Abstract. The p53 oncosuppressor protein regulates mary myoblasts, pRb is hypophosphorylated and prolif- cell cycle checkpoints and apoptosis, but increasing evi- eration stops. However, these cells do not upregulate dence also indicates its involvement in differentiation pRb and have reduced MyoD activity. The transduction and development. We had previously demonstrated of exogenous TP53 or Rb genes in p53-defective myo- that in the presence of differentiation-promoting stim- blasts rescues MyoD activity and differentiation poten- uli, p53-defective myoblasts exit from the cell cycle but tial. Additionally, in vivo studies on the Rb promoter do not differentiate into myocytes and myotubes. To demonstrate that p53 regulates the Rb gene expression identify the pathways through which p53 contributes at transcriptional level through a p53-binding site. to skeletal muscle differentiation, we have analyzed Therefore, here we show that p53 regulates myoblast the expression of a series of genes regulated during differentiation by means of pRb without affecting its myogenesis in parental and dominant–negative p53 cell cycle–related functions. (dnp53)-expressing C2C12 myoblasts. We found that in dnp53-expressing C2C12 cells, as well as in p53Ϫ/Ϫ pri- Key words: p53 • Rb • MyoD • differentiation • muscle Introduction The differentiation of skeletal myoblasts is characterized review, see Wright, 1992).
    [Show full text]