Evolved Repression Overcomes Enhancer Robustness

Ella Preger-Ben Noon; Fred P Davis; David L Stern

doi:10.1016/j.devcel.2016.10.010

Evolved Repression Overcomes Enhancer Robustness

Dev Cell. 2016 Dec 5;39(5):572-584. doi: 10.1016/j.devcel.2016.10.010. Epub 2016 Nov 10.

Authors

Ella Preger-Ben Noon¹, Fred P Davis², David L Stern³

Affiliations

¹ Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: pregere@janelia.hhmi.org.
² Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
³ Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA. Electronic address: sternd@janelia.hhmi.org.

PMID: 27840106
DOI: 10.1016/j.devcel.2016.10.010

Abstract

Biological systems display extraordinary robustness. Robustness of transcriptional enhancers results mainly from clusters of binding sites for the same transcription factor, and it is not clear how robust enhancers can evolve loss of expression through point mutations. Here, we report the high-resolution functional dissection of a robust enhancer of the shavenbaby gene that has contributed to morphological evolution. We found that robustness is encoded by many binding sites for the transcriptional activator Arrowhead and that, during evolution, some of these activator sites were lost, weakening enhancer activity. Complete silencing of enhancer function, however, required evolution of a binding site for the spatially restricted potent repressor Abrupt. These findings illustrate that recruitment of repressor binding sites can overcome enhancer robustness and may minimize pleiotropic consequences of enhancer evolution. Recruitment of repression may be a general mode of evolution to break robust regulatory linkages.

Keywords: enhancer evolution; morphology; repression; robustness; transcription.

MeSH terms

Animals
Animals, Genetically Modified
Base Sequence
Binding Sites / genetics
Body Patterning / genetics
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Drosophila / embryology
Drosophila / genetics*
Drosophila / metabolism
Drosophila Proteins / antagonists & inhibitors
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster / embryology
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism
Enhancer Elements, Genetic*
Epigenetic Repression
Evolution, Molecular*
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Knockout Techniques
Genes, Insect
Genetic Variation
LIM-Homeodomain Proteins / antagonists & inhibitors
LIM-Homeodomain Proteins / genetics
LIM-Homeodomain Proteins / metabolism
Models, Genetic
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

Awh protein, Drosophila
DNA-Binding Proteins
Drosophila Proteins
LIM-Homeodomain Proteins
Nuclear Proteins
Transcription Factors
ab protein, Drosophila
ovo protein, Drosophila