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Locus architecture affects mRNA expression levels in Drosophila embryos

Tara Lydiard-Martin, Meghan Bragdon, Kelly B. Eckenrode, Zeba Wunderlich, Angela H. DePace
doi: https://doi.org/10.1101/005173
Tara Lydiard-Martin
Department of Systems Biology, Harvard Medical School, Boston, MA 02115
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Meghan Bragdon
Department of Systems Biology, Harvard Medical School, Boston, MA 02115
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Kelly B. Eckenrode
Department of Systems Biology, Harvard Medical School, Boston, MA 02115
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Zeba Wunderlich
Department of Systems Biology, Harvard Medical School, Boston, MA 02115
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Angela H. DePace
Department of Systems Biology, Harvard Medical School, Boston, MA 02115
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  • For correspondence: Angela_DePace@hms.harvard.edu
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Abstract

Structural variation in the genome is common due to insertions, deletions, duplications and rearrangements. However, little is known about the ways structural variants impact gene expression. Developmental genes are controlled by multiple regulatory sequence elements scattered over thousands of bases; developmental loci are therefore a good model to test the functional impact of structural variation on gene expression. Here, we measured the effect of rearranging two developmental enhancers from the even-skipped (eve) locus in Drosophila melanogaster blastoderm embryos. We systematically varied orientation, order, and spacing of the enhancers in transgenic reporter constructs and measured expression quantitatively at single cell resolution in whole embryos to detect changes in both level and position of expression. We found that the position of expression was robust to changes in locus organization, but levels of expression were highly sensitive to the spacing between enhancers and order relative to the promoter. Our data demonstrate that changes in locus architecture can dramatically impact levels of gene expression. To quantitatively predict gene expression from sequence, we must therefore consider how information is integrated both within enhancers and across gene loci.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 14, 2014.
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Locus architecture affects mRNA expression levels in Drosophila embryos
Tara Lydiard-Martin, Meghan Bragdon, Kelly B. Eckenrode, Zeba Wunderlich, Angela H. DePace
bioRxiv 005173; doi: https://doi.org/10.1101/005173
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Locus architecture affects mRNA expression levels in Drosophila embryos
Tara Lydiard-Martin, Meghan Bragdon, Kelly B. Eckenrode, Zeba Wunderlich, Angela H. DePace
bioRxiv 005173; doi: https://doi.org/10.1101/005173

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