Abstract：
Cellular homeostasis is constantly challenged by a myriad of extrinsic and intrinsic stressors. To mitigate the stress-induced damage, cells activate transient survival programs. The heat shock response (HSR) is an evolutionarily well-conserved survival program that is activated in response to proteotoxic stress. The HSR encompasses a dual regulation of transcription, characterized by rapid activation of genes encoding molecular chaperones and concomitant global attenuation of non-chaperone genes. Recent genome-wide approaches have delineated the molecular depth of stress-induced transcriptional reprogramming. The dramatic rewiring of gene and enhancer networks is driven by key transcription factors, including heat shock factors (HSFs), that together with chromatin-modifying enzymes remodel the 3D chromatin architecture, determining the selection of either gene activation or repression. Here, we highlight the current advancements of molecular mechanisms driving transcriptional reprogramming during acute heat stress. We also discuss the emerging implications of HSF-mediated stress signaling in the context of physiological and pathological conditions.
摘要：
细胞内稳态不断受到无数外在和内在应激源的挑战。为了减轻应力引起的损伤，细胞激活瞬时生存程序。热休克反应（HSR）是一种进化上保守的生存程序，可响应蛋白毒性应激而激活。HSR包含转录的双重调节，其特征在于编码分子伴侣的基因的快速激活和伴随的非伴侣基因的整体衰减。最近的全基因组方法已经描绘了应激诱导的转录重编程的分子深度。基因和增强子网络的戏剧性重组是由关键转录因子驱动的，包括热休克因子(HSF)，与染色质修饰酶一起重塑3D染色质结构，确定基因激活或抑制的选择。这里,我们重点介绍了在急性热应激期间驱动转录重编程的分子机制的当前进展。我们还讨论了在生理和病理条件下HSF介导的应激信号传导的新含义。
