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Decoupling between activation time and steady-state level in input-output responses.

Giorgio Ravanelli1,2, Kee-Myoung Nam3, Jeremy Gunawardena3

  • 1CRG (Barcelona Collaboratorium for Modelling and Predictive Biology), Barcelona, Spain.

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|May 15, 2026
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Summary
This summary is machine-generated.

This study explores output decoupling in biological systems, where input concentration affects response levels but not activation time. Two mechanisms, rate scale separation and incoherent regulation, explain this phenomenon in gene regulation.

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Area of Science:

  • Systems Biology
  • Molecular Biology
  • Biophysics

Background:

  • Biological processes like gene regulation and cell signaling involve molecular inputs binding to targets, triggering downstream responses.
  • Recent findings indicate that higher transcription factor (TF) concentrations can increase gene transcription without altering activation time, a phenomenon termed output decoupling.

Purpose of the Study:

  • To investigate the mechanisms underlying output decoupling in biological input-output systems.
  • To identify conditions in Markov process models where readout molecule levels change with input concentration, while activation time remains constant.

Main Methods:

  • Utilized Markov process models to simulate molecular binding and readout production.
  • Employed analytical and numerical investigations to analyze system dynamics.
  • Quantified activation time using mean first-passage times.

Main Results:

  • Identified two key mechanisms for output decoupling: rate scale separation and incoherent regulation.
  • Rate scale separation occurs when inputs differentially regulate slow and fast system transitions.
  • Incoherent regulation involves opposing input effects on transitions when rate constants are similar.

Conclusions:

  • Output decoupling is a characteristic feature of incoherent regulation in transcription factor (TF) activity.
  • The findings provide a mechanistic framework for understanding output decoupling in biological input-output systems.
  • Suggests decoupling as a novel characteristic of TF regulatory modes.