Imperial College London
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DR MICHALIS BARKOULAS

Faculty of Natural Sciences, Department of Life Sciences

Reader in Molecular Genetics
 
 
 
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Contact

 

+44 (0)20 7594 5227m.barkoulas

 
 
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Location

 

506Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Barkoulas:2016:10.1371/journal.pgen.1006278,
author = {Barkoulas, M and Vargas, Velazquez AM and Peluffo, AE and Félix, MA},
doi = {10.1371/journal.pgen.1006278},
journal = {PLOS Genetics},
title = {Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis},
url = {http://dx.doi.org/10.1371/journal.pgen.1006278},
volume = {12},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR) binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression.
AU  - Barkoulas,M
AU  - Vargas,Velazquez AM
AU  - Peluffo,AE
AU  - Félix,MA
DO  - 10.1371/journal.pgen.1006278
PY  - 2016///
SN  - 1553-7390
TI  - Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis
T2  - PLOS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1006278
UR  - http://hdl.handle.net/10044/1/40308
VL  - 12
ER  -
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