Expression-based segmentation of the Drosophila genome

Abstract

BACKGROUND: It is generally accepted that gene order in eukaryotes is nonrandom, with adjacent genes often sharing expression patterns across tissues, and that this organization may be important for gene regulation. Here we describe a novel method, based on an explicit probability model instead of correlation analysis, for identifying coordinately expressed gene clusters ('coexpression segments'), apply it to Drosophila melanogaster, and look for epigenetic associations using publicly available data. RESULTS: We find that two-thirds of Drosophila genes fall into multigenic coexpression segments, and that such segments are of two main types, housekeeping and tissue-restricted. Consistent with correlation-based studies, we find that adjacent genes within the same segment tend to be physically closer to each other than to the adjacent genes in different segments, and that tissue-restricted segments are enriched for testis-expressed genes. Our segmentation pattern correlates with Hi-C based physical interaction domains, but segments are generally much smaller than domains. Intersegment regions (including those which do not correspond to physical domain boundaries) are enriched for insulator binding sites. CONCLUSIONS: We describe a novel approach for identifying coexpression clusters that does not require arbitrary cutoff values or heuristics, and find that coexpression of adjacent genes is widespread in the Drosophila genome. Coexpression segments appear to reflect a level of regulatory organization related to, but below that of physical interaction domains, and depending in part on insulator binding.