%0 Journal Article
%T Short-term cold exposure induces persistent epigenomic memory in brown fat.
%A Inoue SI
%A Emmett MJ
%A Lim HW
%A Midha M
%A Richter HJ
%A Celwyn IJ
%A Mehmood R
%A Chondronikola M
%A Klein S
%A Hauck AK
%A Lazar MA
%J Cell Metab
%V 36
%N 8
%D 2024 Aug 6
%M 38889724
%F 31.373
%R 10.1016/j.cmet.2024.05.011
%X Deficiency of the epigenome modulator histone deacetylase 3 (HDAC3) in brown adipose tissue (BAT) impairs the ability of mice to survive in near-freezing temperatures. Here, we report that short-term exposure to mild cold temperature (STEMCT: 15°C for 24 h) averted lethal hypothermia of mice lacking HDAC3 in BAT (HDAC3 BAT KO) exposed to 4°C. STEMCT restored the induction of the thermogenic coactivator PGC-1α along with UCP1 at 22°C, which is greatly impaired in HDAC3-deficient BAT, and deletion of either UCP1 or PGC-1α prevented the protective effect of STEMCT. Remarkably, this protection lasted for up to 7 days. Transcriptional activator C/EBPβ was induced by short-term cold exposure in mouse and human BAT and, uniquely, remained high for 7 days following STEMCT. Adeno-associated virus-mediated knockdown of BAT C/EBPβ in HDAC3 BAT KO mice erased the persistent memory of STEMCT, revealing the existence of a C/EBPβ-dependent and HDAC3-independent cold-adaptive epigenomic memory.