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We show that cold exposure induces temperature\u2010specific changes to the higher\u2010order chromatin and gene expression profiles of human cells. These changes are particularly dramatic at 18\u00b0C, a temperature synonymous with that experienced by patients undergoing controlled deep hypothermia during surgery. Cells exposed to 18\u00b0C exhibit largely nuclear\u2010restricted transcriptome changes. These include the nuclear accumulation of mRNAs encoding components of the negative limbs of the core circadian clock, most notably REV\u2010ERB\u03b1. This response is accompanied by compaction of higher\u2010order 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\u2010induced upregulation of REV\u2010ERB\u03b1 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.<\/jats:p>","DOI":"10.15252\/embj.2020105604","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T04:01:23Z","timestamp":1602216083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Cold\u2010induced chromatin compaction and nuclear retention of clock mRNAs resets the circadian rhythm"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-5917","authenticated-orcid":false,"given":"Harry","family":"Fischl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-369X","authenticated-orcid":false,"given":"David","family":"McManus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9646-910X","authenticated-orcid":false,"given":"Roel","family":"Oldenkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1612-9699","authenticated-orcid":false,"given":"Lothar","family":"Schermelleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-3734","authenticated-orcid":false,"given":"Jane","family":"Mellor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-8200","authenticated-orcid":false,"given":"Aarti","family":"Jagannath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1161-2841","authenticated-orcid":false,"given":"Andr\u00e9","family":"Furger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"BFEMBJ2020105604_CR1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1042\/BJ20060166","volume":"397","author":"MB Al\u2010Fageeh","year":"2006","unstructured":"Al\u2010Fageeh MB, Smales CM (2006) Control and regulation of the cellular responses to cold shock: the responses in yeast and mammalian systems. 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