Temporal Signaling and Information Processing in Chromatin-Mediated Gene Regulation

Chromatin-mediated gene regulation is a key pathway cells use to regulate gene expression in response to internal and external stimuli; however, the full range of dynamic gene expression patterns achievable using chromatin regulation is unknown. Chromatin regulators (CRs) activate or silence genes in an all-or-none fashion and have distinct degrees of epigenetic memory; this behavior can be described via phenomenological models in which cells transition between active and silent states. Using this approach, we demonstrate that repressive CRs without long-term epigenetic memory can filter out high frequency noise, and can be used in autoregulatory loops to control population gene expression profiles. Repressive CRs with long-term memory encode the total duration of their recruitment in the fraction of cells irreversibly silenced, but cannot sustain oscillatory dynamics. Activating CRs can be used in combination with repressive CRs to produce well-known behaviors including adaptation and ultrasensitivity. Additionally, we quantify the ability of CRs to encode the duration of their recruitment in the fraction of cells silenced using an information-theoretic approach, and analyze the effect of input and output noise on the fidelity of CR signaling. Altogether, we describe dynamics of gene regulation achievable by CRs based on phenomenological models of chromatin regulation, demonstrate how they can be used to build complex signaling behaviors, and provide a mathematical formalism for analyzing their ability to transmit information in cells.