Mammalian hibernation: differential gene expression and novel application of epigenetic controls
Mammalian hibernation: differential gene expression and novel application of epigenetic controls
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DOI：
10.1387/ijdb.082643pm
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发表时间：
2009-01-01
影响因子：
0.7
通讯作者：
Storey, Kenneth B.
中科院分区：
文献类型：
--
作者：
Morin, Pier, Jr.;Storey, Kenneth B.
这篇综述重点介绍了哺乳动物冬眠期间基因表达调控机制的最新信息，特别是表观遗传控制在协调转录全局抑制中的潜在作用。冬眠的特点是长时间的深度麻木（当核心体温下降到接近环境温度时），其间穿插着短暂的唤醒期，以恢复体温。进入休眠状态需要协调控制，这些控制强烈抑制并重新确定所有代谢功能的优先级，包括转录和翻译的全局控制。然而，与此同时，选择的冬眠特异性基因在特定转录因子的控制下被上调，支持冬眠状态；这包括编码参与脂质燃料分解代谢和长期细胞保护（如抗氧化剂、伴侣）的蛋白质的基因。我们评估了目前关于冬眠中全球转录抑制的现有信息，并提出表观遗传机制，如DNA甲基化，组蛋白修饰，SUMOylation和sirtuins的作用在冬眠期间的转录抑制中起关键作用。提供翻译抑制的全局控制也发生在冬眠期间，包括核糖体起始和延伸因子的可逆磷酸化控制以及多聚体解离。我们还提供了初步数据，表明在冬眠期间，mRNA转录是通过与microRNA物种的抑制相互作用来调节的，并提供了microRNA在冬眠中差异表达的第一个证据。综上所述，这些机制为冬眠动物提供了多层调控控制，既实现了基因表达的全局抑制，又选择性地增强了实现冬眠表型的基因/蛋白质。
This review highlights current information about the regulatory mechanisms that govern gene expression during mammalian hibernation, in particular the potential role of epigenetic controls in coordinating the global suppression of transcription. Hibernation is characterized by long periods of deep torpor (when core body temperature drops to near ambient) that are interspersed with brief arousal periods back to euthermia. Entry into torpor requires coordinated controls which strongly suppress and reprioritize all metabolic functions, including global controls on both transcription and translation. At the same time, however, selected hibernation-specific genes are up-regulated under the control of specific transcription factors to support the torpid state; this includes genes that encode proteins involved in lipid fuel catabolism and in long term cytoprotection (e.g. antioxidants, chaperones). We evaluate the currently available information on global transcriptional suppression in hibernation and propose that epigenetic mechanisms such as DNA methylation, histone modification, SUMOylation and the actions of sirtuins play crucial roles in transcriptional suppression during torpor. Global controls providing translational suppression also occur during hibernation including reversible phosphorylation control of ribosomal initiation and elongation factors as well as polysome dissociation. We also present initial data that mRNA transcripts are regulated via inhibitory interactions with microRNA species during torpor and provide the first evidence of differential expression of miRNAs in hibernators. When taken together, these mechanisms provide hibernators with multiple layers of regulatory controls that achieve both global repression of gene expression and selected enhancement of genes/proteins that achieve the hibernation phenotype.