Dubay, B.; Muthukumar, R.; Purayil, F. T.; Sundararaja Moorthy, D. K.; Shah, I.; Rajendran, T.; Poulose, M.; Oun, M. A.; Hazzouri, K. M.; Amiri, K. M.

Climate warming is intensifying seasonal heat and drought, raising urgent questions about how long-lived desert plants sustain physiological function across recurrent extremes. In Prosopis cineraria, a native Arabian desert legume tree, we used seasonal Hi-C, transcriptomic, histone-mark, and DNA-methylation profiling at six time points to uncover the underlying mechanisms. We found that during peak heat, chromatin boundaries are selectively weakened and candidate topological domains merge, activating clusters of heat-protective genes enriched for H3K4me3 and H3K27ac. In the cool season, immune and developmental gene regulation is coupled with flowering, consistent with a bet-hedging strategy that shifts reproduction away from lethal heat. At the same time, promoter CHH methylation near transposable elements and reduced H3K4me3/H3K27ac hint at a proactive developmental phase rather than just surviving the stress. Integrating physiological data, we connect chromatin activation to an SA-ABA reciprocal seasonal profile, MIZ1-associated hydrotropism, and Stay-Green-mediated delayed senescence through chlorophyll retention. With Landscape genomics and phylogenetics, we further identified a housekeeping PEPC with a high predicted melting temperature that could sustain a malate-derived carbon supply, buffering metabolism under heat. Together, these findings reveal that reversible epigenetic gating enables desert trees to survive and recover from extreme seasonal stress.