Temporal signaling, population control, and information processing through chromatin-mediated gene regulation

Area of Science:

• Cellular biology
• Synthetic biology
• Systems biology

Background:

• Chromatin regulation controls gene expression in response to stimuli.
• It is increasingly utilized in synthetic biology.
• Cells exhibit stochastic transitions between gene states (active, reversible, irreversible silencing).

Purpose of the Study:

• Develop a mathematical framework to analyze genetic circuits with chromatin regulators responding to temporal signals in mammalian cell populations.
• Investigate responses achievable with duration-dependent signaling by integrating chromatin regulation with gene regulatory motifs.
• Explore the information transmission capabilities of chromatin-mediated gene control.

Main Methods:

• Mathematical modeling of chromatin regulation and gene regulatory motifs (autoregulatory, feedforward loops).
• Analysis of stochastic transitions between gene states (active, reversibly silent, irreversibly silent).
• Information theoretic approach to assess information transmission fidelity.

Main Results:

• Repressive regulators without epigenetic memory can filter noise and tune gene expression fractions in autoregulatory loops.
• Regulators with epigenetic memory can encode signal duration and enable perfect adaptation in feedforward loops.
• All-or-none stochastic silencing allows reliable information transmission in simple genetic circuits.

Conclusions:

• Chromatin-mediated gene control provides a range of complex population responses to temporal signals.
• This mechanism enhances information transmission levels compared to previous gene regulation studies.
• The mathematical framework offers insights into designing synthetic gene circuits with sophisticated behaviors.