Signatures of combinatorial regulation in intrinsic biological noise.
Gene expression is controlled by the action of transcription factors that bind to DNA and influence the rate at which a gene is transcribed. The quantitative mapping between the regulator concentrations and the output of the gene is known as the cis-regulatory input function (CRIF). Here, we show how the CRIF shapes the form of the joint probability distribution of molecular copy numbers of the regulators and the product of a gene. Namely, we derive a class of fluctuation-based relations that relate the moments of the distribution to the derivatives of the CRIF. These relations are useful because they enable statistics of naturally arising cell-to-cell variations in molecular copy numbers to substitute for traditional manipulations for probing regulatory mechanisms. We demonstrate that these relations can distinguish super- and subadditive gene regulatory scenarios (molecular analogs of AND and OR logic operations) in simulations that faithfully represent bacterial gene expression. Applications and extensions to other regulatory scenarios are discussed.
Warmflash
Aryeh
A
James Franck Institute, University of Chicago, Chicago, IL 60637, USA.
Dinner
Aaron R
AR
D003198:Computer Simulation; D004247:DNA / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008957:Models, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
D014157:Transcription Factors; D004247:DNA