RT Journal Article
SR Electronic
T1 Locus architecture affects mRNA expression levels in Drosophila embryos
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 005173
DO 10.1101/005173
A1 Tara Lydiard-Martin
A1 Meghan Bragdon
A1 Kelly B. Eckenrode
A1 Zeba Wunderlich
A1 Angela H. DePace
YR 2014
UL http://biorxiv.org/content/early/2014/05/14/005173.abstract
AB 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.