Heterotrimerization of heat-shock factors 1 and 2 provides a transcriptional switch in response to distinct stimuli.
Organisms respond to circumstances threatening the cellular protein homeostasis by activation of heat-shock transcription factors (HSFs), which play important roles in stress resistance, development, and longevity. Of the four HSFs in vertebrates (HSF1-4), HSF1 is activated by stress, whereas HSF2 lacks intrinsic stress responsiveness. The mechanism by which HSF2 is recruited to stress-inducible promoters and how HSF2 is activated is not known. However, changes in the HSF2 expression occur, coinciding with the functions of HSF2 in development. Here, we demonstrate that HSF1 and HSF2 form heterotrimers when bound to satellite III DNA in nuclear stress bodies, subnuclear structures in which HSF1 induces transcription. By depleting HSF2, we show that HSF1-HSF2 heterotrimerization is a mechanism regulating transcription. Upon stress, HSF2 DNA binding is HSF1 dependent. Intriguingly, when the elevated expression of HSF2 during development is mimicked, HSF2 binds to DNA and becomes transcriptionally competent. HSF2 activation leads to activation of also HSF1, revealing a functional interdependency that is mediated through the conserved trimerization domains of these factors. We propose that heterotrimerization of HSF1 and HSF2 integrates transcriptional activation in response to distinct stress and developmental stimuli.
Sandqvist
Anton
A
Turku Centre for Biotechnology, University of Turku, Abo Akademi University, 20520 Turku, Finland.
Björk
Johanna K
JK
Akerfelt
Malin
M
Chitikova
Zhanna
Z
Grichine
Alexei
A
Vourc'h
Claire
C
Jolly
Caroline
C
Salminen
Tiina A
TA
Nymalm
Yvonne
Y
Sistonen
Lea
L
D000818:Animals; D002460:Cell Line; D004276:DNA, Satellite / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004276:DNA, Satellite; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human