Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
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DOI：
10.1016/j.cmet.2012.01.001
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发表时间：
2012-03-07
期刊：
影响因子：
29
通讯作者：
Zierath, Juleen R.
中科院分区：
文献类型：
--
作者：
Barres, Romain;Yan, Jie;Zierath, Juleen R.
DNA甲基化是控制染色质结构和基因表达的共价生化修饰。运动引起基因表达变化，从而触发骨骼肌的结构和代谢适应。我们确定DNA甲基化是否在运动诱导的基因表达中起作用。急性运动后，健康久坐男性和女性的骨骼肌活检显示全基因组甲基化降低。运动诱导PGC-1 α、PDK4和PPAR-delta的剂量依赖性表达，并在每个各自的启动子上出现显著的低甲基化。同样，小鼠比目鱼肌在离体收缩45分钟后，PGC-1 α、PDK4和PPAR-delta的启动子甲基化显著降低。在L6肌管中，咖啡因暴露诱导基因低甲基化与相应mRNA含量的增加并行。总的来说，我们的研究结果提供了证据，表明急性基因激活与骨骼肌DNA甲基化的动态变化有关，并表明DNA低甲基化是收缩诱导的基因激活的早期事件。
DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1 alpha, PDK4, and PPAR-delta, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1 alpha, PDK4, and PPAR-delta was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.