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A Bioinformatics Analysis of the Arabidopsis Thaliana Epigenome Ikhlak Ahmed

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A Bioinformatics Analysis of the Arabidopsis Thaliana Epigenome Ikhlak Ahmed A bioinformatics analysis of the arabidopsis thaliana epigenome Ikhlak Ahmed To cite this version: Ikhlak Ahmed. A bioinformatics analysis of the arabidopsis thaliana epigenome. Agricultural sciences. Université Paris Sud - Paris XI, 2011. English. NNT : 2011PA112230. tel-00684391 HAL Id: tel-00684391 https://tel.archives-ouvertes.fr/tel-00684391 Submitted on 2 Apr 2012 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. 2011 PhD Thesis Ikhlak Ahmed Laboratoire: CNRS UMR8197 - INSERM U1024 Institut de Biologie de l'ENS(IBENS) Ecole Doctorale : Sciences Du Végétal A Bioinformatics analysis of the Arabidopsis thaliana Epigenome Supervisors: Dr. Chris Bowler and Dr. Vincent Colot Jury Prof. Dao-Xiu Zhou President Prof. Christian Fankhauser Rapporteur Dr. Raphaël Margueron Rapporteur Dr. Chris Bowler Examiner Dr. Vincent Colot Examiner Dr. Allison Mallory Examiner Dr. Michaël Weber Examiner Acknowledgement I express my deepest gratitude to my supervisors Dr. Chris Bowler and Dr. Vincent Colot for the support, advice and freedom that I enjoyed working with them. I am very thankful to Chris Bowler who trusted in me and gave me the opportunity to come here and work in the excellent possible conditions. I have no words to express my thankfulness to Vincent Colot for his enthusiastic supervision and the incredibly valuable sessions we spent together that shaped my understanding of DNA methylation. I am very thankful to my friends Uma Maheswari, Alexis Sarazin, Clara Bourbousse, Stéphanie Drevense who were always there to solve my day-to-day problems. I would also like to thank all the members of the Bowler & Colot groups for their advices, scientific discussions and the moral support they gave me. I also want to thank Sophie de Peindray for her great help. During this work I have collaborated with many colleagues for whom I have great regard, and I wish to extend my warmest thanks to Frédy Barneche, François Roudier and Hadi Quesneville who have helped me with the work. I wish to thank my entire extended family for their love and belief in me especially to my sister, Seema Gull, for her constant efforts to keep us all happy and to take care of the family in my absence. Lastly, and most importantly, I am forever indebted to my parents, AG and papa, for always being there, to care, protect and raise me, their rightful teachings and unconditional love. To them I dedicate this thesis. Table of Contents CHAPTER I .......................................................................................................... 4 INTRODUCTION TO CHROMATIN AND CHROMATIN-level GENOME ORGANISATION .................................................................................................. 4 Introduction ............................................................................................................................................................... 5 Histone post-translational modifications .................................................................................................................. 9 DNA Methylation ..................................................................................................................................................... 12 Genomic Context of DNA Methylation .................................................................................................................... 13 Establishment and maintenance of DNA methylation ............................................................................................ 16 Regulation of DNA methylation ............................................................................................................................... 21 Methods to identify DNA methylation .................................................................................................................... 23 The bioinformatics of epigenome data analysis ...................................................................................................... 27 R and Bioconductor support .................................................................................................................................... 31 Analysis of microarray ChIP-on-chip data ................................................................................................................ 34 Peak Finding ............................................................................................................................................................. 37 Aims and organisation of the thesis ........................................................................................................................ 40 References: .............................................................................................................................................................. 41 CHAPTER II ....................................................................................................... 51 GENOME-WIDE EVIDENCE FOR LOCAL DNA METHYLATION SPREADING FROM SMALL RNA TARGETED SEQUENCES IN ARABIDOPSIS ...................................... 51 Introduction ............................................................................................................................................................. 52 Materials and Methods .......................................................................................................................................... 55 DNA methylation analysis ........................................................................................................................................ 56 Results ..................................................................................................................................................................... 57 Discussion ................................................................................................................................................................ 64 References .............................................................................................................................................................. 65 Supplementary Information .................................................................................................................................... 67 Additional Methods ................................................................................................................................................. 82 Data visualization and downstream analysis ........................................................................................................... 89 CHAPTER III ...................................................................................................... 97 INTEGRATIVE EPIGENOMIC MAPPING DEFINES FOUR MAIN CHROMATIN STATES IN ARABIDOPSIS ................................................................................... 97 Introduction ............................................................................................................................................................. 98 Results ................................................................................................................................................................... 101 Discussion .............................................................................................................................................................. 105 Materials and methods .......................................................................................................................................... 108 References ............................................................................................................................................................ 109 Supplementary ..................................................................................................................................................... 111 Review process file ................................................................................................................................................ 121 Additional Methods ............................................................................................................................................... 128 Combinatorial Analysis .......................................................................................................................................... 128 Co-association ........................................................................................................................................................ 135 Cluster Analysis ...................................................................................................................................................... 136 Cluster Validity and clustering tendency ............................................................................................................... 140 CHAPTER IV .................................................................................................... 145 SPATIAL & TEMPORAL DYNAMICS IN HISTONE H2BUB CHROMATIN MARK DURING LIGHT DRIVEN
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