Rouble Andrew N, Hawkins Liam J, Storey Kenneth B
Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada.
Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada.
J Therm Biol. 2018 May;74:71-76. doi: 10.1016/j.jtherbio.2018.03.013. Epub 2018 Mar 15.
The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) is a well-known model for studying hibernation. While in a torpid state, these animals globally suppress energy expensive processes, while supporting specialized pathways necessary for survival. Lysine acetyltransferases (KATs) play a crucial role in modulating the expression and activity of a wide-variety of cellular pathways and processes, and therefore, may play a role during hibernation when the cell is shifting to an energy conservative, cytoprotective state. Here we measured protein levels of four KATs (CBP, PCAF, GCN5L2, HAT1), total histone acetyltransferase (HAT) activity, and the levels of acetylation of histone H3 lysine 9 (H3K9ac), in multiple tissues across the torpor-arousal cycle. Our results show a tissue-specific response of KATs, particularly in the adipose tissues where specific KATs (PCAF and GCN5L2), HAT activity, and H3K9ac increased in the metabolically active BAT while HAT1, HAT activity and H3K9ac decreased in WAT. Liver showed significant increases in the KAT PCAF whereas skeletal muscle had decreased CBP and GCN5L2. Both liver and skeletal muscle showed no change in HAT activity and H3K9me3 increased in muscle during torpor. Together, these results suggest KATs may play specialized roles in the different tissues of the ground squirrel to contribute to the hibernator phenotype.
十三条纹地松鼠（Ictidomys tridecemlineatus）是研究冬眠的著名模型。在蛰伏状态下，这些动物会全面抑制耗能过程，同时维持生存所需的特定途径。赖氨酸乙酰转移酶（KATs）在调节多种细胞途径和过程的表达及活性方面发挥着关键作用，因此，在细胞转向能量保守的细胞保护状态的冬眠期间可能发挥作用。在此，我们测量了整个蛰伏-觉醒周期中多个组织中四种KATs（CBP、PCAF、GCN5L2、HAT1）的蛋白质水平、总组蛋白乙酰转移酶（HAT）活性以及组蛋白H3赖氨酸9（H3K9ac）的乙酰化水平。我们的结果显示KATs存在组织特异性反应，特别是在脂肪组织中，特定的KATs（PCAF和GCN5L2）、HAT活性以及H3K9ac在代谢活跃的褐色脂肪组织中增加，而在白色脂肪组织中HAT1、HAT活性和H3K9ac降低。肝脏中KAT PCAF显著增加，而骨骼肌中CBP和GCN5L2减少。肝脏和骨骼肌的HAT活性均无变化，且在蛰伏期间肌肉中H3K9me3增加。总之，这些结果表明KATs可能在十三条纹地松鼠的不同组织中发挥特定作用，以促成冬眠动物的表型。
