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Cold-induced chromatin compaction and nuclear retention of clock mRNAs resets the circadian rhythm

ABSTRACT: Cooling patients to sub-physiological temperatures is an integral part of modern medicine. We show that cold exposure induces temperature-specific changes to the higher-order chromatin and gene expression profiles of human cells. These changes are particularly dramatic at 18°C, a temperature synonymous with that experienced by patients undergoing controlled deep-hypothermia during surgery. Cells exposed to 18°C exhibit largely nuclear-restricted transcriptome changes. These include the nuclear accumulation of transcripts of genes of the negative limbs of the core circadian clock, most notably REV-ERBα. This response is accompanied by compaction of higher-order chromatin and hindrance of mRNPs from engaging nuclear pores. Rewarming reverses chromatin compaction and releases the transcripts into the cytoplasm, triggering a pulse of negative limb gene proteins that resets the circadian clock. We show that cold-induced upregulation of REV-ERBα is sufficient to trigger this resetting. Our findings uncover principles of the cellular cold-response that must be considered for current and future applications involving therapeutic deep-hypothermia.

ORGANISM(S): Homo sapiens Drosophila melanogaster

PROVIDER: GSE137003 | GEO | 2020/09/30

REPOSITORIES: GEO

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