Self-organized epigenetic signal processing in active chromatin
摘要
Active histone marks turn over rapidly in open chromatin, yet their states do not simply track the instantaneous regulatory input and can retain information about prior stimulation. We develop a theoretical framework that separates this external input a(τ) from a state-dependent spatial amplification G(m), through which existing marks reshape local factor availability. A sufficiently steep increase in G(m) generates two thresholds that partition inputs into OFF, MEMORY, and ON regimes, governing mark erasure, history-dependent maintenance, and establishment. In a microscopic polymer model with epigenetic switching, marked chromatin and mobile factors self-organize into a localized reaction hub, thereby generating the required nonlinear G(m). Measured directly from microscopic configurations, this constitutive relation enables quantitative predictions of deterministic regime boundaries, first-passage statistics, recovery after perturbation, and frequency-dependent hysteresis without additional fitting. The resulting response architecture allows strong inputs to establish a high-mark state, weaker inputs to maintain it while limiting off-target spreading, and repeated inputs to be integrated over time. These results identify self-organized spatial feedback as a minimal mechanism for epigenetic signal processing in active chromatin.
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