A comparison of nucleosome organization in Drosophila cell lines.

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PloS one, ISSN: 1932-6203, Vol: 12, Issue: 6, Page: e0178590

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10.1371/journal.pone.0178590; 10.1371/journal.pone.0178590.g003; 10.1371/journal.pone.0178590.t003; 10.1371/journal.pone.0178590.g002; 10.1371/journal.pone.0178590.g005; 10.1371/journal.pone.0178590.g006; 10.1371/journal.pone.0178590.t001; 10.1371/journal.pone.0178590.t002; 10.1371/journal.pone.0178590.g001; 10.1371/journal.pone.0178590.g004
Rebecca L. Martin; John Maiorano; Greg J. Beitel; John F. Marko; Graham McVicker; Yvonne N. Fondufe-Mittendorf; Sue Cotterill
Public Library of Science (PLoS); Figshare
Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; nucleosome organization; Drosophila melanogaster; cell lines; gene expression; nucleosomes; Biophysics; Medicine; Cell Biology; Genetics; Molecular Biology; Developmental Biology; Cancer; Hematology; 110309 Infectious Diseases; Computational Biology; 69999 Biological Sciences not elsewhere classified; Drosophila melanogaster cell lines; cell line-specific nucleosome enrichment; Drosophila cell lines; gene expression profiles; genome-wide nucleosome; impact gene expression; nucleosomal; Drosophila cell lines Changes; transcription factor binding sites; DNA; cell type specification; reconstituted chromatin; Drosophila tissue-specific cell lines; transcription factor binding motifs; genome influence chromatin structure; Biochemistry, Biophysics, and Structural Biology; Genetics and Genomics
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Changes in the distribution of nucleosomes along the genome influence chromatin structure and impact gene expression by modulating the accessibility of DNA to transcriptional machinery. However, the role of genome-wide nucleosome positioning in gene expression and in maintaining differentiated cell states remains poorly understood. Drosophila melanogaster cell lines represent distinct tissue types and exhibit cell-type specific gene expression profiles. They thus could provide a useful tool for investigating cell-type specific nucleosome organization of an organism's genome. To evaluate this possibility, we compared genome-wide nucleosome positioning and occupancy in five different Drosophila tissue-specific cell lines, and in reconstituted chromatin, and then tested for correlations between nucleosome positioning, transcription factor binding motifs, and gene expression. Nucleosomes in all cell lines were positioned in accordance with previously known DNA-nucleosome interactions, with helically repeating A/T di-nucleotide pairs arranged within nucleosomal DNAs and AT-rich pentamers generally excluded from nucleosomal DNA. Nucleosome organization in all cell lines differed markedly from in vitro reconstituted chromatin, with highly expressed genes showing strong nucleosome organization around transcriptional start sites. Importantly, comparative analysis identified genomic regions that exhibited cell line-specific nucleosome enrichment or depletion. Further analysis of these regions identified 91 out of 16,384 possible heptamer sequences that showed differential nucleosomal occupation between cell lines, and 49 of the heptamers matched one or more known transcription factor binding sites. These results demonstrate that there is differential nucleosome positioning between these Drosophila cell lines and therefore identify a system that could be used to investigate the functional significance of differential nucleosomal positioning in cell type specification.