Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock. We show that pause-release of RNA polymerase II (Pol II) is a universal mechanism regulating gene transcription in stressed cells, while enhancers are activated at the level of Pol II recruitment. Moreover, besides functioning as conventional promoter-binding transcription factors, HSF1 and HSF2 bind to stress-induced enhancers to trigger Pol II pause-release from poised gene promoters. Importantly, HSFs act at distinct genes and enhancers in a stress type-specific manner. HSF1 binds to many chaperone genes upon oxidative and heat stress but activates them only in heat-shocked cells. Under oxidative stress, HSF1 localizes to a unique set of promoters and enhancers to trans-activate oxidative stress-specific genes. Taken together, we show that HSFs function as multi-stress-responsive factors that activate distinct genes and enhancers when encountering changes in temperature and redox state.

Talin 1 (TLN1) is best known for its role at focal adhesions, where it activates β-integrin receptors and transmits mechanical stimuli to the actin cytoskeleton. Interestingly, the localization of TLN1 is not restricted to the focal adhesions, but its function in other cellular compartments remains poorly understood. By utilizing both biochemical and confocal microscopy analyses, we show that TLN1 localizes to the nucleus and that it strongly interacts with the chromatin. Importantly, depletion of endogenous TLN1 results in extensive changes in the gene expression profile of human breast epithelial cells. To determine the impact of nuclear TLN1 on gene regulation, we expressed a TLN1 fusion protein containing a nuclear localization signal. Our results revealed that nuclear TLN1 regulates a specific subset of the TLN1-dependent genes. Taken together, we show that apart from localizing at the plasma membrane and cytoplasm, TLN1 also resides in the nucleus where it functions in the regulation of gene expression.