EPIGENETIC CONTROL OF TRANSCRIPTIONAL PLASTICITY UNDER MULTI-STRESS ENVIRONMENTAL CONDITIONS

Abstract

Transcriptional plasticity is a key biological mechanism through which organisms can dynamically regulate gene expression to changing environmental conditions. This adaptive ability is especially vital during times of stress that is; during rapid and synchronized responses by molecules, survival and resilience are acquired. Although there is an increasing interest in epigenetic regulation, the mechanisms of transcriptional plasticity in the combined or multi-stress conditions are poorly understood. Specifically, it remains unclear how particular stress signals are combined at the epigenetic level to tune gene expression programs. Our hypothesis in this work is that multi-stress exposure causes the coordinated epigenetic remodeling in increasing transcriptional plasticity by modulating chromatin accessibility and gene-regulatory network dynamics. To examine this, a multi-omics (combining transcriptomic (RNA-seq), epigenomic (DNA methylation profiling), and chromatin state (ChIP-seq of histone modifications) analyses were used under regulated single and combined stresses. The analysis of differential gene expression showed that when stress is exposed in multi-stress, the stress-responsive transcriptional activity of cells increased significantly as compared to when the same cells were subjected to a single stress treatment. At the same time, the epigenetic profiling revealed a significant drop in promoter methylation and enrichment of activating histone marks (e.g., H3K27ac, H3K4me3) of core regulatory genes, with reference to increased chromatin accessibility. Integrated multi-omics analysis also revealed closely orchestrated regulatory networks of stress-responsive transcription factors and signaling pathways such as MAPK and reactive oxygen species (ROS)-mediated signaling. These results are an indication that the effect of multi-stress condition is a synergism of the effect of individual stresses and not additive. All in all, this paper offers proof that under complicated environmental circumstances, epigenetic processes are of prime importance in concerting transcriptional plasticity. Results emphasize how the chromatin-level regulation may be paramount to adaptive responses and provide a new understanding of the molecular foundations of stress resilience, which can be subsequently utilized in agriculture, environmental biology, and biomedical research.