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Proc Natl Acad Sci U S A 2017 Jun 06;11423:5854-5861. doi: 10.1073/pnas.1610611114.
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Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development.

Cary GA , Cheatle Jarvela AM , Francolini RD , Hinman VF .

Sea stars and sea urchins are model systems for interrogating the types of deep evolutionary changes that have restructured developmental gene regulatory networks (GRNs). Although cis-regulatory DNA evolution is likely the predominant mechanism of change, it was recently shown that Tbrain, a Tbox transcription factor protein, has evolved a changed preference for a low-affinity, secondary binding motif. The primary, high-affinity motif is conserved. To date, however, no genome-wide comparisons have been performed to provide an unbiased assessment of the evolution of GRNs between these taxa, and no study has attempted to determine the interplay between transcription factor binding motif evolution and GRN topology. The study here measures genome-wide binding of Tbrain orthologs by using ChIP-sequencing and associates these orthologs with putative target genes to assess global function. Targets of both factors are enriched for other regulatory genes, although nonoverlapping sets of functional enrichments in the two datasets suggest a much diverged function. The number of low-affinity binding motifs is significantly depressed in sea urchins compared with sea star, but both motif types are associated with genes from a range of functional categories. Only a small fraction (∼10%) of genes are predicted to be orthologous targets. Collectively, these data indicate that Tbr has evolved significantly different developmental roles in these echinoderms and that the targets and the binding motifs in associated cis-regulatory sequences are dispersed throughout the hierarchy of the GRN, rather than being biased toward terminal process or discrete functional blocks, which suggests extensive evolutionary tinkering.

PubMed ID: 28584099
PMC ID: PMC5468674
Article link: Proc Natl Acad Sci U S A

Genes referenced: LOC100887844 LOC575170 tbr1
Antibodies: tbr Ab1

GEO Series: GSE89862: NCBI
GSE89863: NCBI
References [+] :
Anders, HTSeq--a Python framework to work with high-throughput sequencing data. 2015, Pubmed