HSF1 is required for cellular adaptation to daily temperature fluctuations

Area of Science:

• Cellular biology
• Molecular biology
• Evolutionary biology

Background:

• The heat shock response (HSR) is a fundamental cellular adaptation to heat stress.
• Heat shock transcription factor 1 (HSF1) and HSF3 regulate HSR in vertebrate endotherms.
• Egg-laying mammals (monotremes) have lower body temperature regulation capacity compared to other mammals.

Purpose of the Study:

• To investigate the roles of HSF1 and HSF3 in cellular adaptation to temperature fluctuations.
• To compare the HSR-inducing potential of HSF1 and HSF3 from different vertebrate groups.
• To determine the specific function of HSF1 in human cell adaptation to daily temperature variations.

Main Methods:

• Comparative analysis of HSF1 and HSF3 from monotremes and birds.
• Functional assays in HSF1-null human cells.
• Gene expression analysis of HSF1-target genes.

Main Results:

• Monotreme HSF1 and HSF3 can maximally induce HSR, while bird HSF1 or HSF3 have this potential individually.
• HSF1, but not HSF3, from vertebrates restored thermal resistance in HSF1-null human cells.
• HSF1's protective function was linked to the upregulation of specific target genes, independent of heat shock protein induction.

Conclusions:

• HSF1 plays a distinct role in adapting cells to environments with daily temperature fluctuations.
• The functional divergence of vertebrate HSF genes is associated with the evolution of homeothermic capacity.
• HSF1 is essential for human cell proliferation and survival under fluctuating thermal conditions.