PgmNr D194: Natural variation in binding site affinity controls stochastic gene expression in the fly eye.

Authors:
C. Anderson 1 ; C. Zhou 1 ; I. Reiss 1 ; A. Cho 1 ; H. Siddiqi 1 ; B. Mormann 2 ; C. Avelis 1 ; E. Roberts 1 ; J. Taylor 1 ; D. Vasiliauskas 3 ; R. Johnston 1


Institutes
1) Johns Hopkins University, Baltimore, MD; 2) New York University, New York, NY; 3) Université Paris Diderot, Paris, France.


Keyword: cis-regulatory logic

Abstract:

Stochastic mechanisms are critical to diversify cell fates during development. How the proportions of randomly determined cell fates is controlled is poorly understood. The stochastic on/off expression of the transcription factor Spineless (Ss) in R7 photoreceptors determines the patterning of two subtypes in the fly eye. Our studies of natural variation revealed a single nucleotide polymorphism (SNP) in a non-coding DNA element in the ss gene locus that lowers the percentage of Ss on cells (“low ss SNP”). This SNP lies within a binding site for the zinc finger transcriptional repressor Klumpfuss (Klu) and increases Klu binding affinity. Klu acts in R7s to lower the ratio of Ss on to off cells: loss of klu function causes more R7s to express Ss whereas increasing Klu levels causes a decrease in the number of Ss-expressing R7s. Thus, the levels of Klu protein are converted into a ratio of Ss on/off cells. Our data suggest that stochastic on/off gene expression is controlled by threshold levels of trans factors bound to low affinity sites.



Flybase Genetic Index:
1. FlyBase gene symbol: Ss; FBgn: FBgn0003513
2. FlyBase gene symbol: Klu; FBgn: FBgn0013469