Controlling transcriptional programs for cellular adaptation by chromatin regulation

Abstract

Gene expression is dynamically reprogrammed during growth control and stress responses, which are two key processes of cellular adaptation. Single-gene studies suggest that gene regulatory patterns of the two processes commonly show high environmental responsiveness, but contrast in terms of regulatory flexibility. Our whole-genome analysis shows that the growth and stress genes are associated with activated and repressed chromatin, respectively, which can modulate the responsiveness of promoters and help balance regulatory flexibility and fidelity. Stochastic modeling of critical nucleosomes at specific promoter regions enables rapid induction of genes during stress responses by activating repressed chromatin. Conversely, activating histone modifications may contribute to regulatory fidelity for precise growth control by common transcription factors. Nucleosome eviction and modification loss lead to an intermediate chromatin state. The combinatorial role of nucleosome organization and modification is central to the balanced control of gene expression programs for stress responses and efficient growth. These regulatory mechanisms can also contribute to evolutionary adaptation.