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Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development.

ABSTRACT: 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.

SUBMITTER: Cary GA

PROVIDER: S-EPMC5468674 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development.

Cary Gregory A GA Cheatle Jarvela Alys M AM Francolini Rene D RD Hinman Veronica F VF

Proceedings of the National Academy of Sciences of the United States of America 20170601 23

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 <i>cis</i>-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 compari ...[more]

PMID: 28584099

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Project description:Despite almost 40 years of molecular genetics research in Escherichia coli a major fraction of its Transcription Start Sites (TSSs) are still unknown, limiting therefore our understanding of the regulatory circuits that control gene expression in this model organism. RegulonDB (http://regulondb.ccg.unam.mx/) is aimed at integrating the genetic regulatory network of E. coli K12 as an entirely bioinformatic project up till now. In this work, we extended its aims by generating experimental data at a genome scale on TSSs, promoters and regulatory regions. We implemented a modified 5' RACE protocol and an unbiased High Throughput Pyrosequencing Strategy (HTPS) that allowed us to map more than 1700 TSSs with high precision. From this collection, about 230 corresponded to previously reported TSSs, which helped us to benchmark both our methodologies and the accuracy of the previous mapping experiments. The other ca 1500 TSSs mapped belong to about 1000 different genes, many of them with no assigned function. We identified promoter sequences and type of sigma factors that control the expression of about 80% of these genes. As expected, the housekeeping sigma(70) was the most common type of promoter, followed by sigma(38). The majority of the putative TSSs were located between 20 to 40 nucleotides from the translational start site. Putative regulatory binding sites for transcription factors were detected upstream of many TSSs. For a few transcripts, riboswitches and small RNAs were found. Several genes also had additional TSSs within the coding region. Unexpectedly, the HTPS experiments revealed extensive antisense transcription, probably for regulatory functions. The new information in RegulonDB, now with more than 2400 experimentally determined TSSs, strengthens the accuracy of promoter prediction, operon structure, and regulatory networks and provides valuable new information that will facilitate the understanding from a global perspective the complex and intricate regulatory network that operates in E. coli.

Dataset Information

Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development.

Publications

Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development.

Similar Datasets

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