Widespread transcriptional responses to the thermal stresses are prewired in human 3D genome

Abstract

Temperature changes is one of the most common environmental stress that consequences with massive phenotypic responses for almost all the life forms. The dysregulation of heat shock (HS) response genes had been found associated with various severe diseases, including cancer. Although the HS response has been well studied in animal cells, it remains elusive whether or not the cells response to cold shock (CS) similarly. Here, we comprehensively compared the changes of gene expression, epigenetic marks (H3K4me3 and H3K27ac), binding of genome architecture proteins (CTCF, SMC3 and Pol II) and chromatin conformation after HS and CS in human cells. Widespread expression change was observed after both HS and CS. Remarkably, we identified distinguished characters in those thermal stress responded genes at nearly all levels of chromatin architecture, i.e, the compartment, topological associated domain, chromatin loops and transcription elongation regulators, in the normal condition. However, the global chromatin architecture remains largely stable after both CS and HS. Interestingly, the thermal stresses responded genes are prone to spatial clustering even before the temperature changes. Our data suggested that the transcriptional response to the thermal stresses maybe independent to the changes of the high-level chromatin architecture, e.g., compartments and TAD, while it may be more dependent on the precondition of the chromatin and epigenetic settings at the normal condition.