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      Dynamic reprogramming of chromatin accessibility during Drosophila embryo development

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          Abstract

          Background

          The development of complex organisms is believed to involve progressive restrictions in cellular fate. Understanding the scope and features of chromatin dynamics during embryogenesis, and identifying regulatory elements important for directing developmental processes remain key goals of developmental biology.

          Results

          We used in vivo DNaseI sensitivity to map the locations of regulatory elements, and explore the changing chromatin landscape during the first 11 hours of Drosophila embryonic development. We identified thousands of conserved, developmentally dynamic, distal DNaseI hypersensitive sites associated with spatial and temporal expression patterning of linked genes and with large regions of chromatin plasticity. We observed a nearly uniform balance between developmentally up- and down-regulated DNaseI hypersensitive sites. Analysis of promoter chromatin architecture revealed a novel role for classical core promoter sequence elements in directing temporally regulated chromatin remodeling. Another unexpected feature of the chromatin landscape was the presence of localized accessibility over many protein-coding regions, subsets of which were developmentally regulated or associated with the transcription of genes with prominent maternal RNA contributions in the blastoderm.

          Conclusions

          Our results provide a global view of the rich and dynamic chromatin landscape of early animal development, as well as novel insights into the organization of developmentally regulated chromatin features.

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          Most cited references43

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          A gene complex controlling segmentation in Drosophila.

          E B Lewis (1978)
          The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal development. The state of repression of at least four of these genes is controlled by cis-regulatory elements and a separate locus (Polycomb) seems to code for a repressor of the complex. The wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element.
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            High-resolution mapping and characterization of open chromatin across the genome.

            Mapping DNase I hypersensitive (HS) sites is an accurate method of identifying the location of genetic regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. We employed high-throughput sequencing and whole-genome tiled array strategies to identify DNase I HS sites within human primary CD4+ T cells. Combining these two technologies, we have created a comprehensive and accurate genome-wide open chromatin map. Surprisingly, only 16%-21% of the identified 94,925 DNase I HS sites are found in promoters or first exons of known genes, but nearly half of the most open sites are in these regions. In conjunction with expression, motif, and chromatin immunoprecipitation data, we find evidence of cell-type-specific characteristics, including the ability to identify transcription start sites and locations of different chromatin marks utilized in these cells. In addition, and unexpectedly, our analyses have uncovered detailed features of nucleosome structure.
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              Homeobox genes and axial patterning.

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                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central
                1465-6906
                1465-6914
                2011
                11 May 2011
                : 12
                : 5
                : R43
                Affiliations
                [1 ]Department of Genome Sciences, University of Washington, Foege S310A, 1705 NE Pacific Street, Box 355065, Seattle, WA 98195, USA
                [2 ]Genomics and Life Sciences Divisions, Lawrence Berkeley National Laboratory, One Cyclotron Road, MS 84-171, Berkeley, California 94720, USA
                Article
                gb-2011-12-5-r43
                10.1186/gb-2011-12-5-r43
                3219966
                21569360
                bdfc4cee-9795-44be-b3b6-4a6255d886bf
                Copyright ©2011 Thomas et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 February 2011
                : 21 March 2011
                : 11 May 2011
                Categories
                Research

                Genetics
                Genetics

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