Protein sequestration versus Hill-type repression in circadian clock models

TL;DR

This paper compares protein sequestration and Hill-type repression mechanisms in circadian clock models, revealing fundamental differences in rhythm generation, robustness, and period regulation across species.

Contribution

It provides a detailed analysis of how different transcriptional repression mechanisms affect circadian clock dynamics and their biological implications.

Findings

Protein sequestration models differ from Hill-type models in rhythm conditions.

Repression mechanisms influence robustness and period of oscillators.

Species-specific differences relate to repression types.

Abstract

Circadian (~24hr) clocks are self-sustained endogenous oscillators with which organisms keep track of daily and seasonal time. Circadian clocks frequently rely on interlocked transcriptional- translational feedback loops to generate rhythms that are robust against intrinsic and extrinsic perturbations. To investigate the dynamics and mechanisms of the intracellular feedback loops in circadian clocks, a number of mathematical models have been developed. The majority of the models use Hill functions to describe transcriptional repression in a way that is similar to the Goodwin model. Recently, a new class of models with protein sequestration-based repression has been introduced. Here, we discuss how this new class of models differs dramatically from those based on Hill-type repression in several fundamental aspects: conditions for rhythm generation, robust network designs and the periods of coupled oscillators. Consistently, these fundamental properties of circadian clocks also differ among Neurospora, Drosophila, and mammals depending on their key transcriptional repression mechanisms (Hill-type repression or protein sequestration). Based on both theoretical and experimental studies, this review highlights the importance of careful modeling of transcriptional repression mechanisms in molecular circadian clocks.