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A bioinformatics analysis of the arabidopsis thaliana epigenomeAhmed, Ikhlak 14 November 2011 (has links) (PDF)
Eukaryotic genomes are packed into the confines of the nucleus through a nucleoproteic structure called chromatin. Chromatin is a dynamic structure that can respond to developmental or environmental cues to regulate and orchestrate the functions of the genome. The fundamental unit of chromatin, the nucleosome, consists of a protein octamer, which contains two molecules of each of the core histone proteins (H2A, H2B, H3, H4), around which 147 bp of DNA is wrapped. The post-translational modifications (PTMs) of histones and methylation of the cytosine residues in DNA (DNA methylation) constitute primary epigenomic markers that dynamically alter the interaction of DNA with nucleosomes and participate in the regulation and control access to the underlying DNA. The main objective of my thesis was to understand the spatial and temporal dynamics of chromatin states in Arabidopsis by investigating on a genome-wide scale, patterns of DNA methylation and a set of well-characterized histone post-translational modifications. DNA methylation, a hallmark of epigenetic inactivation and heterochromatin in both plants and mammals, is largely confined to transposable elements and other repeat sequences. I show in this thesis that in Arabidopsis, methylated TE sequences having no or few matching siRNAs, and therefore unlikely to be targeted by the RNA-directed DNA methylation (RdDM) machinery, acquire DNA methylation through spreading from adjacent siRNA-targeted regions. Further, I propose that this spreading of DNA methylation through promoter regions can explain, at least in part, the negative impact of siRNA-targeted TE sequences on neighbouring gene expression. In a second part, I have contributed to integrative analysis of DNA methylation and eleven histone PTMs. I have shown through combinatorial and cluster analysis that the Arabidopsis epigenome shows simple principles of organisation and can be distinguished into four primary types of chromatin that preferentially index active genes, repressed genes, TEs, and intergenic regions. Finally, in a third part, I integrated epigenomics with transcriptome data at three different time points in a developmental window to investigate the temporal dynamics of chromatin states in response to an external stimulus. This used the light-induced transcriptional response as a paradigm to assess the impact of histone H2B monoubiquitination (H2Bub), and showed that this PTM is associated with active transcription and implicated in the selective fine-tuning of gene expression. Taken together, the work presented here contributes significantly to our understanding of the spatial organisation of chromatin states in plants, its dynamic nature and how it can contribute to allow plants to respond to a signal from the environment.
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A bioinformatics analysis of the arabidopsis thaliana epigenome / Une analyse bioinformatique de l'Epigénome d’Arabidopsis thalianaAhmed, Ikhlak 14 November 2011 (has links)
Les génomes nucléaires eucaryotes sont empaquetés au sein d’une structure nucléoprotéique appelée chromatine et dont l’unité fondamentale est le nucléosome. Celui-ci est composé d’un octamère d’histones, contenant deux molécules de chacune des histones H2A, H2B, H3 et H4, autour duquel 147 pb d’ADN sont enroulées. Les modifications post-traductionnelles (PTMs) des histones et de l’ADN (méthylation des cytosines) constituent des marqueurs épigénomiques primaires qui participent à la régulation et au contrôle de l’accessibilité des différentes régions du génome. Ainsi, la chromatine forme une structure dynamique influencée par les changements environnementaux et développementaux et contribue à orchestrer diverses fonctions du génome. L’objectif principal de ma thèse était de caractériser l’organisation spatiale et la dynamique temporelle des états chromatiniens chez Arabidopsis par des approches à l’échelle du génome permettant l’étude des profils de méthylation de l’ADN et d’un ensemble de modifications post-traductionnelles des histones. La méthylation de l’ADN, une marque caractéristique de l’inactivation épigénétique et de l’hétérochromatine chez les plantes et les mammifères, est largement confinée aux séquences répétées, dont les éléments transposables (TEs). Par mon travail de thèse, j’ai montré que chez Arabidopsis les séquences de TEs faiblement méthylées ou non associées à des petits ARN interférents (siRNAs), donc potentiellement non régulées par la machinerie de RNA-directed DNA methylation (RdDM), peuvent acquérir une méthylation de l’ADN par diffusion à partir de séquences adjacentes ciblées par les siRNAs. Cette diffusion de la méthylation de l’ADN sur des régions promotrices pourrait expliquer, au moins en partie, l’impact négatif des TEs associés à des siRNAs sur l’expression des gènes à proximité immédiate. Dans une seconde partie de ma thèse, j’ai contribué à l’analyse intégrée de la méthylation de l’ADN et de onze modifications des histones. L’utilisation d’analyses combinatoires et en cluster m’a permis de montrer que l’épigénome d’Arabidopsis présente des principes simples d’organisation. En effet, ces analyses nous ont conduit à distinguer quatre états fondamentaux de la chromatine chez Arabidopsis, préférentiellement associés aux gènes actifs, aux gènes inactifs, aux TEs et aux régions intergéniques. Dans une troisième partie, j’ai intégré des données épigénomiques et transcriptomiques obtenues à différents temps afin d’étudier les dynamiques temporelles des états chromatiniens en réponse à un stimulus externe, la première exposition à la lumière des plantules suite à la germination. Ces travaux nous ont permis de montrer que la monoubiquitination de l’histone H2B participe à la modulation fine et sélective des changements rapides de l’expression de gènes. L’ensemble du travail présenté contribue à une meilleure compréhension de l’organisation de la chromatine le long du génome des plantes et de la dynamique des états chromatiniens en réponse aux changements de l’environnement. / Eukaryotic genomes are packed into the confines of the nucleus through a nucleoproteic structure called chromatin. Chromatin is a dynamic structure that can respond to developmental or environmental cues to regulate and orchestrate the functions of the genome. The fundamental unit of chromatin, the nucleosome, consists of a protein octamer, which contains two molecules of each of the core histone proteins (H2A, H2B, H3, H4), around which 147 bp of DNA is wrapped. The post-translational modifications (PTMs) of histones and methylation of the cytosine residues in DNA (DNA methylation) constitute primary epigenomic markers that dynamically alter the interaction of DNA with nucleosomes and participate in the regulation and control access to the underlying DNA. The main objective of my thesis was to understand the spatial and temporal dynamics of chromatin states in Arabidopsis by investigating on a genome-wide scale, patterns of DNA methylation and a set of well-characterized histone post-translational modifications. DNA methylation, a hallmark of epigenetic inactivation and heterochromatin in both plants and mammals, is largely confined to transposable elements and other repeat sequences. I show in this thesis that in Arabidopsis, methylated TE sequences having no or few matching siRNAs, and therefore unlikely to be targeted by the RNA-directed DNA methylation (RdDM) machinery, acquire DNA methylation through spreading from adjacent siRNA-targeted regions. Further, I propose that this spreading of DNA methylation through promoter regions can explain, at least in part, the negative impact of siRNA-targeted TE sequences on neighbouring gene expression. In a second part, I have contributed to integrative analysis of DNA methylation and eleven histone PTMs. I have shown through combinatorial and cluster analysis that the Arabidopsis epigenome shows simple principles of organisation and can be distinguished into four primary types of chromatin that preferentially index active genes, repressed genes, TEs, and intergenic regions. Finally, in a third part, I integrated epigenomics with transcriptome data at three different time points in a developmental window to investigate the temporal dynamics of chromatin states in response to an external stimulus. This used the light-induced transcriptional response as a paradigm to assess the impact of histone H2B monoubiquitination (H2Bub), and showed that this PTM is associated with active transcription and implicated in the selective fine-tuning of gene expression. Taken together, the work presented here contributes significantly to our understanding of the spatial organisation of chromatin states in plants, its dynamic nature and how it can contribute to allow plants to respond to a signal from the environment.
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