Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks

From Murray Wiki
Revision as of 15:54, 26 January 2019 by Murray (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigationJump to search
Title Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks
Authors Enoch Yeung, Aaron J. Dy, Kyle B. Martin, Andrew H. Ng, Domitilla Del Vecchio, James L. Beck, James J. Collins, Richard M. Murray
Source Cell Systems, 5(1):11–24.e12, 2017
Abstract Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem-oriented genes. Orientation affects gene expression whether one or both genes are induced. We postulate that transcriptional interference in divergent and tandem genes, mediated by supercoiling, can explain differences in expression and validate this hypothesis through modeling and in vitro supercoiling relaxation experiments. Treatment with gyrase abrogated intergenic context effects, bringing expression levels within 30% of each other. We rebuilt the toggle switch with convergent genes, taking advantage of supercoiling effects to improve threshold detection and switch stability.
Type Journal paper
Tag yeu+17-cellsys
ID 2017e
Flags Biocircuits