Heat shock factors HSF1 and HSF2 are stress-inducible transcription factors, which also participate in a myriad of developmental, physiological and pathological processes, such as gametogenesis and cancer progression. HSFs have been previously shown to regulate distinct transcriptional networks so that they selectively choose the target genes in response to variable signals, to promote oncogenic and developmental processes. Intriguingly, by mapping active transcription sites with the high-resolution next-generation sequencing methods, we have found that acute heat stress induces HSF1-dependent activation of both genes and enhancers. These results indicate that HSFs can utilize the complexity of the human genome in their transcriptional networks, composed of signal-specific selection of genes, encoding mRNAs, and regulatory sequences, encoding eRNAs. However, the role of HSFs in stress-induced differentiation, and the networks therein, is not known. Our future aim is to unravel how HSF1 and HSF2 influence the phenotypic plasticity of cells that are exposed to stress during differentiation.


Selected publications:

Molecular Mechanisms of Heat Shock Factors in Cancer.
Puustinen MC, Sistonen L.
Cells. 2020 May 12;9(5):E1202. doi: 10.3390/cells9051202.

Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion.
Joutsen J, Da Silva AJ, Luoto JC, Budzynski MA, Nylund AS, de Thonel A, Concordet JP, Mezger V, Sabéran-Djoneidi D, Henriksson E, Sistonen L.
Cell Rep. 2020 Jan 14;30(2):583-597.e6. doi: 10.1016/j.celrep.2019.12.037.

HSF1 at a glance.
Vihervaara A, Sistonen L.
J Cell Sci. 2014 Jan 15;127(Pt 2):261-6.

Regulation of HSF1 function in the heat stress response: implications in aging and disease.
Anckar J, Sistonen L.
Annu Rev Biochem. 2011;80:1089-115.

Regulation of the members of the mammalian heat shock factor family.
Björk JK, Sistonen L.
FEBS J. 2010 Oct;277(20):4126-39.

Heat shock factors: integrators of cell stress, development and lifespan.
Åkerfelt M, Morimoto RI, Sistonen L.
Nat Rev Mol Cell Biol. 2010 Aug;11(8):545-55.