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Heterotrimerization of heat-shock factors 1 and 2 provides a transcriptional switch in response to distinct stimuli.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2009 Mar; Vol. 20 (5), pp. 1340-7. Date of Electronic Publication: 2009 Jan 07. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line
DNA, Satellite metabolism
DNA-Binding Proteins genetics
DNA-Binding Proteins physiology
Heat Shock Transcription Factors
Heat-Shock Proteins genetics
Heat-Shock Proteins physiology
Humans
Male
Mice
Testis metabolism
Transcription Factors genetics
Transcription Factors physiology
Transcription, Genetic
DNA-Binding Proteins metabolism
Heat-Shock Proteins metabolism
Heat-Shock Response physiology
Transcription Factors metabolism
Transcriptional Activation
Subjects
Details
- Language :
- English
- ISSN :
- 1939-4586
- Volume :
- 20
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 19129477
- Full Text :
- https://doi.org/10.1091/mbc.E08-08-0864