Comparative analysis of regulatory information and circuits across distant species

Abstract

SummaryDespite the large evolutionary distances, metazoan species show remarkable commonalities, which has helped establish fly and worm as model organisms for human biology1,2. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. We mapped the genome-wide binding locations of 165 human, 93 worm, and 52 fly transcription-regulatory factors (RFs) generating a total of 1,019 data sets from diverse cell-types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous RF families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding in the regulatory underpinnings of model organism biology and how these relate to human biology, development, and disease.

Genome-wide map of regulatory interactions in the human genome

“…These neurons tended to contain TSS regions and may represent high-occupancy target (HOT) regions, genomic loci bound by multiple TFs that often mark the promoters of highly expressed genes (Moorman et al 2006;Gerstein et al 2010;Negre et al 2011;Yip et al 2012). We found that HOT regions, as determined by Boyle and colleagues were significantly enriched in long-range interactions (P = 5.9 3 10 À62 , Fisher's exact test) and that HOT regions had a strong preference to interact with other HOT regions (P = 4.5 3 10 À271 , Fisher's exact test) (Boyle et al 2014). Taken together these findings support the model that DNA looping brings active promoters into distinct nuclear subcompartments termed ''transcription factories.…”

Bioinformatics Reveal Five Lineages of Oleosins and the Mechanism of Lineage Evolution Related to Structure/Function from Green Algae to Seed Plants

“…No appreciable pattern of sequence similarity or changes or existence and numbers of the regulatory motifs abscisic acid response element, gibberellin-responsive element response element, low-temperature responsive element, skinhead-1 binding element, and/or antioxidant-response element were found in the 500, 1,000, and 2,000 bp upstream of the coding sequences of SL2 and T8 oleosin genes. Our noncommittal finding reflects the current insufficient knowledge of the mechanism of changes in regulatory motifs in gene promoters leading to the evolutionary alteration of cell/tissue expression in multicellular organisms (Boyle et al, 2014).…”

A novel small molecule that disrupts a key event during the oocyte-to-embryo transition inC. elegans

“…6A). At the peak significance cut-off defined by the modENCODE project (Boyle et al, 2014), we identified 1259 coding genes with LET-607 binding sites within 1.5 kb of the transcription start site (Gene Expression Omnibus, accession number GSE84419). Gene Ontology (GO) analysis of the subset of these candidates with both 100× binding enrichment and a binding site within 500 bp (GEO, GSE84419) identified several …”