Cited by 176Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationChromosomal and Genetic Variations

Deep conservation of the enhancer regulatory code in animals

Wong, Emily S., Zheng, Dawei, Tan, Siew Z., Bower, Neil I., Garside, Victoria, Vanwalleghem, Gilles, Gaiti, Federico, Scott, Ethan +5 more·2020·Science

Abstract

Enhancer function, from sponges to humans: Identifying the function of enhancers, DNA regions that help to regulate gene expression and evolve rapidly, has been difficult. This area of research has been hampered by the difficultly in identifying functional conservation. Wong et al. now show that despite low sequence conservation, enhancer function is strongly conserved through the animal kingdom (see the Perspective by Harmston). Transgenic expression of sponge enhancers in zebrafish and mice demonstrates that these sequences can drive cell type–specific gene expression across species. These results suggest an unexpectedly deep level of conservation of gene regulation across the animal kingdom maintained over the course of metazoan evolution. Science , this issue p. eaax8137 ; see also p. 657

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Crossref · 10.1126/science.aax8137

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  • No known enhancers are completely conserved at the base level across the animal kingdom.

    “In terms of their sequence, there are no known enhancers that are completely conserved at the base level across the animal kingdom [101].”
  • Homologous enhancers in a pair of distantly related species can retain their function in the non-host organism despite differences in DNA sequence.

    “Consistent with this, homologous enhancers in a pair of distantly related species can retain their function in the non-host organism despite differences in DNA sequence [101, 110, 111].”
  • Enhancer conservation is typically modular, commonly preserving the sets of binding sites for the required transcription factors, but often not their exact sequence and orientation.

    “Instead, enhancer conservation is typically “modular”, commonly preserving the sets of binding sites for the required TFs, but often not their exact sequence and orientation [101–109].”

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References 91 · Cited by 176

Authors
Wong, E. S., Zheng, D., Tan, S. Z., Bower, N. I., Garside, V., Vanwalleghem, G., Gaiti, F., Scott, E., Hogan, B. M., Kikuchi, K., McGlinn, E., Francois, M., & Degnan, B. M.
Affiliations
  • The University of Queensland (AU)
  • Victor Chang Cardiac Research Institute (AU)
  • Australian Regenerative Medicine Institute (AU)
  • Institute for Molecular Biosciences, University of Queensland, Brisbane, Australia.
Corresponding author
  • Wong, Emily S.
  • Zheng, Dawei
  • Tan, Siew Z.
  • Degnan, Bernard M.
Venue
Science
Published
2020-11-06
Volume
370
Issue
6517
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W3095586809
Cited by
176
References
91
Citations by year
2026: 28 · 2025: 31 · 2024: 36 · 2023: 29 · 2022: 24 · 2021: 26 · 2020: 2
FWCI
6.58
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Australian Research Council (DE160100755, DP160100573, FL110100044, DP200100250)
  • National Health and Medical Research Council (AP1111169, APP1107643)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
enhancers, enhancer function, gene regulatory evolution, transgene expression, cell type-specific gene expression, animal evolution, sequence conservation, zebrafish, mice
MeSH terms
Animals, Base Sequence, Enhancer Elements, Genetic, Humans, Porifera, Transcription Factors, Zebrafish, Conserved Sequence, Gene Expression Regulation, Developmental, Chromatin Immunoprecipitation, Mice, LIM-Homeodomain Proteins

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