4.5 Article

The Mediator subunit MED12 promotes formation of HSF1 condensates on heat shock response element arrays in heat-shocked cells

Journal

FEBS LETTERS
Volume 597, Issue 13, Pages 1702-1717

Publisher

WILEY
DOI: 10.1002/1873-3468.14617

Keywords

heat shock; HSF1; MED12; phase separation; reporter array; transcription

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Upon heat shock, HSF1 binds to HSEs in the promoters of HSP-encoding genes and recruits Mediator. The transcriptional regulators may be concentrated in phase-separated condensates around the promoters. Using an experimental system, it was demonstrated that MED12 is concentrated in HSF1 condensates and plays an important role in their formation.
Upon heat shock, activated heat shock transcription factor 1 (HSF1) binds to the heat shock response elements (HSEs) in the promoters of mammalian heat shock protein (HSP)-encoding genes and recruits the preinitiation complex and coactivators, including Mediator. These transcriptional regulators may be concentrated in phase-separated condensates around the promoters, but they are too minute to be characterized in detail. We herein established HSF1(-/-) mouse embryonic fibroblasts harbouring HSP72-derived multiple HSE arrays and visualized the condensates of fluorescent protein-tagged HSF1 with liquid-like properties upon heat shock. Using this experimental system, we demonstrate that endogenous MED12, a subunit of Mediator, is concentrated in artificial HSF1 condensates upon heat shock. Furthermore, the knockdown of MED12 markedly reduces the size of condensates, suggesting an important role for MED12 in HSF1 condensate formation.

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