Healthy proteome, i.e. maintenance of protein homeostasis (proteostasis), is vital for life. A tightly orchestrated regulation of cell identity is critical for all multicellular organisms. Cells' ability to remodel their identity is determined by the genes that are transcribed at a given time during the lifespan. In addition to physiological stimuli, various external stresses influence the cellular plasticity programs. Recently, we discovered that the key stress-inducible transcription factors HSF1 and HSF2 drive distinct genes and enhancers in a stress-type specific manner, when exposed to, for example, oxidative stress or thermal stress. Here, we investigate whether these factors drive transcription of specific enhancers, i.e. eRNAs, also during cell differentiation. Further, we will reveal the regulation of HSF-dependent cell fate decisions under physiological and pathological conditions, especially cancer, where cell differentiation programs and proteostasis are severely disrupted.

2023

2027