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2016 ; 166
(1
): 234-44
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Information Integration and Energy Expenditure in Gene Regulation
#MMPMID27368104
Estrada J
; Wong F
; DePace A
; Gunawardena J
Cell
2016[Jun]; 166
(1
): 234-44
PMID27368104
show ga
The quantitative concepts used to reason about gene regulation largely derive
from bacterial studies. We show that this bacterial paradigm cannot explain the
sharp expression of a canonical developmental gene in response to a regulating
transcription factor (TF). In the absence of energy expenditure, with regulatory
DNA at thermodynamic equilibrium, information integration across multiple TF
binding sites can generate the required sharpness, but with strong constraints on
the resultant "higher-order cooperativities." Even with such integration, there
is a "Hopfield barrier" to sharpness; for n TF binding sites, this barrier is
represented by the Hill function with the Hill coefficient n. If, however, energy
is expended to maintain regulatory DNA away from thermodynamic equilibrium, as in
kinetic proofreading, this barrier can be breached and greater sharpness
achieved. Our approach is grounded in fundamental physics, leads to testable
experimental predictions, and suggests how a quantitative paradigm for eukaryotic
gene regulation can be formulated.