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

Area of Science:

• Systems Biology
• Biophysics
• Molecular Biology

Background:

• Biological processes involve molecular inputs binding to targets, triggering downstream responses.
• Gene regulation by transcription factors (TFs) can exhibit output decoupling, where higher TF concentrations increase transcription without altering activation time.

Purpose of the Study:

• Investigate mechanisms of output decoupling in Markov process models.
• Identify conditions where steady-state readout levels change with input concentration, but activation time remains constant.

Main Methods:

• Utilized analytical and numerical investigations of Markov process models.
• Modeled readout molecule production downstream of ligand binding.

Main Results:

• Identified two mechanisms for output decoupling: rate scale separation and incoherent regulation.
• Rate scale separation involves input differentially regulating slow and fast system transitions.
• Incoherent regulation involves input affecting two transitions with opposing effects on readout production.

Conclusions:

• Output decoupling can arise from rate scale separation or incoherent regulation.
• Incoherent regulation, a plausible TF regulatory mode, may be characterized by output decoupling.
• Provides a framework for understanding output decoupling in input-output systems.