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Genome-Wide Characterization of RNA Polymerase II Behavior During Transcription Termination and Upon UV-B Stress Akos Gyenis

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Genome-Wide Characterization of RNA Polymerase II Behavior During Transcription Termination and Upon UV-B Stress Akos Gyenis Genome-wide characterization of RNA polymerase II behavior during transcription termination and upon UV-B stress Akos Gyenis To cite this version: Akos Gyenis. Genome-wide characterization of RNA polymerase II behavior during transcription termination and upon UV-B stress. Genomics [q-bio.GN]. Université de Strasbourg, 2012. English. NNT : 2012STRAJ056. tel-01124075 HAL Id: tel-01124075 https://tel.archives-ouvertes.fr/tel-01124075 Submitted on 6 Mar 2015 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 Santé IGBMC - CNRS UMR 7104 - Inserm U 964 THÈSE présentée par: Akos Gyenis Soutenue le: 19 décembre 2012 Pour obtenir le grade de : Docteur de l’Université de Strasbourg Discipline/ Spécialité: Aspects moléculaires et cellulaires de la biologie Etudes génomiques de la dynamique de l’ARN polymérase II pendant l’étape de terminaison de la transcription et après un stress causé par les UV-B (Genome-wide characterization of RNA polymerase II behavior during transcription termination and upon UV-B stress) THÈSE dirigée par: Dr. Laszlo Tora Institut de génétique et de biologie moléculaire et cellulaire, Strasbourg RAPPORTEURS: Dr. Olivier Bensaude Institut de biologie de l’école normale supérieure, Paris Dr. Matthieu Gerard Institut de biologie et de technologies de Saclay Dr. Evi Soutoglou Institut de génétique et de biologie moléculaire et cellulaire, Strasbourg Contents Contents ............................................................................................................ 2 Acknowledgement............................................................................................. 5 List of abbreviations .......................................................................................... 6 Résumé de thèse ............................................................................................... 9 INTRODUCTION ............................................................................................... 20 Chapter one: RNA polymerase II regulation and pause during transcription . 21 I. The expression of genetic information................................................................................... 21 1. DNA dependent RNA polymerases ..................................................................................... 21 A. Structure of Pol II ........................................................................................................... 23 B. Carboxyl-terminal domain of Pol II ................................................................................. 24 C. Posttranslational modifications of CTD .......................................................................... 25 II. RNA polymerase II transcription cycle.................................................................................... 31 2. Transcription initiation ...................................................................................................... 31 D. Core promoter elements ............................................................................................... 31 E. General transcription factors ......................................................................................... 34 F. Sequential assembly of the PIC complex ........................................................................ 36 G. Activation dependent transcription and coactivators ..................................................... 37 a) Mediator complex...................................................................................................... 37 b) Upstream stimulatory activity (USA) .......................................................................... 38 c) Chromatin remodeling and modifications .................................................................. 38 3. Promoter escape ............................................................................................................... 40 4. Early elongation................................................................................................................. 41 5. Pol II pause ........................................................................................................................ 42 H. Factors contributing in Pol II pause establishment ......................................................... 44 I. Possible roles of Pol II pause .......................................................................................... 47 J. Promoter associated RNAs............................................................................................. 49 6. Transcription elongation .................................................................................................... 50 K. Factors to diminish Pol II pause during elongation ......................................................... 50 d) P-TEFb and DSIF ......................................................................................................... 50 e) TFIIS ........................................................................................................................... 52 f) TFIIF ........................................................................................................................... 53 g) Elongin complex ......................................................................................................... 53 h) The ELL family ............................................................................................................ 54 i) CSB ............................................................................................................................ 55 L. Elongation factors with chromatin remodeling ability .................................................... 55 j) SWI/SNF .................................................................................................................... 55 k) Chd1 .......................................................................................................................... 56 l) FACT and Spt6 ............................................................................................................ 56 M. Elongation factors which maintain histone modifications ........................................... 57 7. Transcription termination and 3’ end processing ............................................................... 57 N. 3’ end processing of pre-mRNA ...................................................................................... 58 O. Different 3’ end processing and termination pathway on short, none-polyadenylated transcripts ............................................................................................................................. 59 P. Transcription termination I: Torpedo model .................................................................. 60 Q. Transcription termination II: Allosteric/anti-terminator model....................................... 61 R. Chromatin remodeling factors at the 3’ end of genes..................................................... 62 8. Pol II pause downstream from 3’-end of genes .................................................................. 63 RESULTS I. ........................................................................................................ 65 III. Genome-wide characterization of Pol II pause downstream from 3’ end of genes.............. 65 IV. Publication I....................................................................................................................... 66 V. Publication II. ........................................................................................................................ 67 VI. DISCUSSION I. .................................................................................................................... 68 Chapter two: The fate of RNA polymerase II transcription upon UVB irradiation ........................................................................................................ 73 VII. Transcription is blocked by alterations in the DNA structure .............................................. 73 9. Ultraviolet light.................................................................................................................. 74 S. UV-induced DNA damage .............................................................................................. 75 T. DNA double strand breaks ............................................................................................. 77 10. Persistent blocks initiate transcription coupled repair processes.................................... 78 U. Nucleotide excision repair (NER) .................................................................................... 78 m) CSB is a key element of TCR / damage recognition ................................................. 79 n) TCR factor recruitment / damage verification............................................................. 80 o) Role of TFIIH complex in TCR ...................................................................................... 81 p) Late steps of TCR
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