Abstract
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 melanogastercell 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.
Document Type
Article
Publication Date
6-1-2017
Digital Object Identifier (DOI)
https://doi.org/10.1371/journal.pone.0178590
Funding Information
This project was funded by grant F31 GM098037 from the National Institute of General Medical Sciences; Grant MCB 1517986 from the National Science foundation; Grant R01-ES024478 from the National Institute of Environmental Health and Grant U54-CA193419 (CR-PS-OC) from the National Cancer Institute.
Related Content
All nucleosome sequencing raw data generated during and/or analyzed during the current study are available from the NIH GEO repository database (accession numbers GSE49526, GSE85584).
Repository Citation
Martin, Rebecca L.; Maiorano, John; Beitel, Greg J.; Marko, John F.; McVicker, Graham; and Fondufe-Mittendorf, Yvonne N., "A Comparison of Nucleosome Organization in Drosophila Cell Lines" (2017). Molecular and Cellular Biochemistry Faculty Publications. 111.
https://uknowledge.uky.edu/biochem_facpub/111
S1 Fig. Mononucleosomal fragments from all cell lines show similar fragment size distribution.
journal.pone.0178590.s002.pdf (3605 kB)
S2 Fig. Nucleosome profiles along arbitrary Drosophila genomic regions maintain features between cell lines.
Notes/Citation Information
Published in PLOS ONE, v. 12, 6, e0178590, p. 1-23.
© 2017 Martin et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.