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表观遗传沉默因子在休眠沙漠蛙肌肉中富集。

Epigenetic silencers are enriched in dormant desert frog muscle.

作者信息

Hudson Nicholas J, Lonhienne T G A, Franklin Craig E, Harper Gregory S, Lehnert S A

机构信息

CSIRO Livestock Industries, Brisbane, Qld, Australia.

出版信息

J Comp Physiol B. 2008 Aug;178(6):729-34. doi: 10.1007/s00360-008-0261-0. Epub 2008 Mar 28.

Abstract

Green-striped burrowing frogs, Cyclorana alboguttata, survive droughts by entering a metabolic depression called aestivation, characterised by a reduction in resting oxygen consumption by 80%. Aestivation in C. alboguttata is manifest by transcriptional silencing of skeletal muscle bioenergetic genes, such as NADH ubiquinone oxidoreductase 1, ATP synthase and superoxide dismutase 2. In this study, we hypothesised that aestivation is associated with epigenetic change in frog muscle. We assessed mRNA transcript abundance of seven genes that code for proteins with established roles in epigenetically-mediated gene silencing [transcriptional co-repressor SIN3A, DNA (cytosine-5-) methyltransferase 1, methyl CpG binding protein 2, chromodomain helicase DNA binding protein 4, histone binding protein rbbp4, histone deacetylase 1 and nuclear receptor co-repressor 2] using qRT-PCR. These seven genes showed a modest (1.1-3.5-fold) but coordinated upregulation in 6-month aestivating muscle. This reached significance for SIN3A and DNA cytosine-5-methyltransferase 1 in standard pair-wise comparisons (p < 0.05), and the candidates as a whole when analysed by Fisher's combined probability test (p < 0.01). These data are consistent with the hypothesis that the transcriptional silencing and metabolic depression that occurs during seasonal dormancy are associated with chromatin remodelling, and present a novel example of an environmentally induced epigenetic modification in an adult vertebrate.

摘要

绿纹穴居蛙(Cyclorana alboguttata)通过进入一种称为夏眠的代谢抑制状态来度过干旱期,其特征是静息耗氧量降低80%。白氏绿纹穴居蛙的夏眠表现为骨骼肌生物能量基因的转录沉默,如NADH泛醌氧化还原酶1、ATP合酶和超氧化物歧化酶2。在本研究中,我们假设夏眠与青蛙肌肉中的表观遗传变化有关。我们使用qRT-PCR评估了七个基因的mRNA转录本丰度,这些基因编码的蛋白质在表观遗传介导的基因沉默中具有既定作用[转录共抑制因子SIN3A、DNA(胞嘧啶-5-)甲基转移酶1、甲基CpG结合蛋白2、染色体结构域解旋酶DNA结合蛋白4、组蛋白结合蛋白rbbp4、组蛋白脱乙酰基酶1和核受体共抑制因子2]。这七个基因在6个月夏眠期的肌肉中呈现出适度(1.1 - 3.5倍)但协同的上调。在标准的成对比较中,SIN3A和DNA胞嘧啶-5-甲基转移酶1达到了显著水平(p < 0.05),当通过Fisher联合概率检验进行分析时,这些候选基因作为一个整体达到了显著水平(p < 0.01)。这些数据与以下假设一致,即在季节性休眠期间发生的转录沉默和代谢抑制与染色质重塑有关,并提供了一个成年脊椎动物中环境诱导表观遗传修饰的新例子。

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