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Plasticity of the cis-Regulatory Input Function of a Gene

Summary: Plasticity of the cis-Regulatory Input
Function of a Gene
Avraham E. Mayo¤
, Yaakov Setty, Seagull Shavit, Alon Zaslaver, Uri Alon*
Departments of Molecular Cell Biology and Physics of Complex Systems, The Weizmann Institute of Science, Rehovot, Israel
The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-
regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What
determines the form of an input function, and how variable is it with respect to mutations? To address this, we employ
the well-characterized lac operon of Escherichia coli, which has an elaborate input function, intermediate between
Boolean AND-gate and OR-gate logic. We mapped in detail the input function of 12 variants of the lac promoter, each
with different point mutations in the regulator binding sites, by means of accurate expression measurements from
living cells. We find that even a few mutations can significantly change the input function, resulting in functions that
resemble Pure AND gates, OR gates, or single-input switches. Other types of gates were not found. The variant input
functions can be described in a unified manner by a mathematical model. The model also lets us predict which functions
cannot be reached by point mutations. The input function that we studied thus appears to be plastic, in the sense that
many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs.
Citation: Mayo AE, Setty Y, Shavit S, Zaslaver A, Alon U (2006) Plasticity of the cis-regulatory input function of a gene. PLoS Biol 4(4): e45.
Much of the computation performed by transcription
networks occurs in the DNA cis-regulatory region (CRR) of


Source: Alon, Uri - Departments of Molecular Cell Biology & Physics of Complex Systems, Weizmann Institute of Science


Collections: Biology and Medicine