PDF(Pubmed)
Abstract：
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.
摘要：
棕色脂肪组织（BAT）中表观基因组调节剂组蛋白脱乙酰酶3（HDAC3）的缺乏会损害小鼠在接近冰点的温度下生存的能力。这里,我们报告说，短期暴露于温和的低温（STEMCT：15°C持续24小时）避免了暴露于4°C的BAT中缺乏HDAC3（HDAC3BATKO）的小鼠的致死性体温过低。STEMCT在22°C时恢复了产热共活化剂PGC-1α和UCP1的诱导，在缺乏HDAC3的BAT中严重受损，UCP1或PGC-1α的缺失可防止STEMCT的保护作用。值得注意的是,这种保护持续了7天。小鼠和人BAT的短期冷暴露诱导转录激活剂C/EBPβ，独一无二，STEMCT后7天保持高位。在HDAC3BATKO小鼠中，腺相关病毒介导的BATC/EBPβ敲低消除了STEMCT的持久性记忆，揭示了C/EBPβ依赖性和HDAC3依赖性冷适应性表观基因组记忆的存在。
