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      Integrative epigenomic mapping defines four main chromatin states in Arabidopsis

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          Abstract

          Post-translational modification of histones and DNA methylation are important components of chromatin-level control of genome activity in eukaryotes. However, principles governing the combinatorial association of chromatin marks along the genome remain poorly understood. Here, we have generated epigenomic maps for eight histone modifications (H3K4me2 and 3, H3K27me1 and 2, H3K36me3, H3K56ac, H4K20me1 and H2Bub) in the model plant Arabidopsis and we have combined these maps with others, produced under identical conditions, for H3K9me2, H3K9me3, H3K27me3 and DNA methylation. Integrative analysis indicates that these 12 chromatin marks, which collectively cover ∼90% of the genome, are present at any given position in a very limited number of combinations. Moreover, we show that the distribution of the 12 marks along the genomic sequence defines four main chromatin states, which preferentially index active genes, repressed genes, silent repeat elements and intergenic regions. Given the compact nature of the Arabidopsis genome, these four indexing states typically translate into short chromatin domains interspersed with each other. This first combinatorial view of the Arabidopsis epigenome points to simple principles of organization as in metazoans and provides a framework for further studies of chromatin-based regulatory mechanisms in plants.

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          Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning.

          Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences. Recent genomic studies in Arabidopsis thaliana have revealed that many endogenous genes are methylated either within their promoters or within their transcribed regions, and that gene methylation is highly correlated with transcription levels. However, plants have different types of methylation controlled by different genetic pathways, and detailed information on the methylation status of each cytosine in any given genome is lacking. To this end, we generated a map at single-base-pair resolution of methylated cytosines for Arabidopsis, by combining bisulphite treatment of genomic DNA with ultra-high-throughput sequencing using the Illumina 1G Genome Analyser and Solexa sequencing technology. This approach, termed BS-Seq, unlike previous microarray-based methods, allows one to sensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts. Here we describe methylation on previously inaccessible components of the genome and analyse the DNA methylation sequence composition and distribution. We also describe the effect of various DNA methylation mutants on genome-wide methylation patterns, and demonstrate that our newly developed library construction and computational methods can be applied to large genomes such as that of mouse.
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            Identification of functional elements and regulatory circuits by Drosophila modENCODE.

            To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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              Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

              We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.
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                Author and article information

                Journal
                EMBO J
                The EMBO Journal
                Nature Publishing Group
                0261-4189
                1460-2075
                18 May 2011
                12 April 2011
                12 April 2011
                : 30
                : 10
                : 1928-1938
                Affiliations
                [1 ]simpleInstitut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique (CNRS) UMR8197, Institut National de la Santé et de la Recherche Médicale (INSERM) U1024 , Paris, France
                [2 ]simpleAgroParisTech/Institut National de la Recherhe Agronomique (INRA), UMR518 Mathématiques et Informatiques Appliquées , Paris, France
                [3 ]simpleInstitut de Biologie Moléculaire des Plantes, CNRS UPR2357, Université de Strasbourg , Strasbourg, France
                [4 ]simpleUnité de Recherche en Génomique Végétale, UMR8114 INRA/CNRS/Université d'Evry Val d'Essonne (UEVE) , Evry, France
                Author notes
                [a ]Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, INSERM U1024, 46 rue d'Ulm, 75230 Paris Cedex 05, France. Tel.: +33 014 432 3538; Fax: +33 014 432 3935; E-mail: roudier@ 123456biologie.ens.fr
                [b ]Institut de Biologie de l'Ecole Normale Supérieure, CNRS UMR8197, INSERM U1024, 46 rue d'Ulm, 75230 Paris Cedex 05, France. Tel.: +33 014 432 3538; Fax: +33 014 432 3935; E-mail: colot@ 123456biologie.ens.fr
                Article
                emboj2011103
                10.1038/emboj.2011.103
                3098477
                21487388
                9e323506-6146-4ee7-947f-0fd0d87bff2e
                Copyright © 2011, European Molecular Biology Organization

                This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

                History
                : 23 November 2010
                : 10 March 2011
                Categories
                Article

                Molecular biology
                histone modifications,dna methylation,chromatin,epigenome,arabidopsis
                Molecular biology
                histone modifications, dna methylation, chromatin, epigenome, arabidopsis

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