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Deep conservation of the enhancer regulatory code in animals

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  • Emily S. Wong, University of Queensland, Victor Chang Cardiac Research Institute, University of New South Wales
  • ,
  • Dawei Zheng, Victor Chang Cardiac Research Institute
  • ,
  • Siew Z. Tan, University of Queensland
  • ,
  • Neil I. Bower, University of Queensland
  • ,
  • Victoria Garside, Monash University
  • ,
  • Gilles Vanwalleghem
  • Federico Gaiti, University of Queensland
  • ,
  • Ethan Scott, University of Queensland
  • ,
  • Benjamin M. Hogan, University of Queensland, University of Melbourne
  • ,
  • Kazu Kikuchi, Victor Chang Cardiac Research Institute
  • ,
  • Edwina McGlinn, Monash University
  • ,
  • Mathias Francois, University of Queensland, University of Sydney
  • ,
  • Bernard M. Degnan, University of Queensland

Interactions of transcription factors (TFs) with DNA regulatory sequences, known as enhancers, specify cell identity during animal development. Unlike TFs, the origin and evolution of enhancers has been difficult to trace. We drove zebrafish and mouse developmental transcription using enhancers from an evolutionarily distant marine sponge. Some of these sponge enhancers are located in highly conserved microsyntenic regions, including an Islet enhancer in the Islet-Scaper region. We found that Islet enhancers in humans and mice share a suite of TF binding motifs with sponges, and that they drive gene expression patterns similar to those of sponge and endogenous Islet enhancers in zebrafish. Our results suggest the existence of an ancient and conserved, yet flexible, genomic regulatory syntax that has been repeatedly co-opted into cell type-specific gene regulatory networks across the animal kingdom.

Original languageEnglish
Article numbereaax8137
Publication statusPublished - 6 Nov 2020
Externally publishedYes

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