PropertyValue
?: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 mRNAs encoding components 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 reset the circadian clock. We show that cold-induced upregulation of REV-ERBα is sufficient to trigger this reset. Our findings uncover principles of the cellular cold response that must be considered for current and future applications involving therapeutic deep hypothermia.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.15252/embj.2020105604
?:journal
  • The_EMBO_journal
?:license
  • cc-by
?:pmid
?:pmid
  • 33034091.0
?:publication_isRelatedTo_Disease
?:source
  • Medline
?:title
  • Cold-induced chromatin compaction and nuclear retention of clock mRNAs resets the circadian rhythm.
?:type
?:year
  • 2020-10-09

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