Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading
Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading
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DOI：
10.1152/ajpcell.00075.2009
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发表时间：
2009-07-01
影响因子：
5.5
通讯作者：
Baldwin, Kenneth M.
中科院分区：
文献类型：
--
作者：
Pandorf, Clay E.;Haddad, Fadia;Baldwin, Kenneth M.
潘德福CE， hadad F, Wright C, Bodell PW, Baldwin KM。快、慢骨骼肌纤维中肌球蛋白重链基因组蛋白的差异表观遗传修饰和对肌肉卸载的反应。[J] .中国生物医学工程学报，2009,31(5):557 - 557。首次发表于2009年4月15日；doi: 10.1152 / ajpcell.00075.2009。-染色质生物学的最新进展增强了我们对基因调控的理解。现在人们普遍认识到，基因调控依赖于细胞核中包装基因的组蛋白的翻译后修饰。已知活性基因与组蛋白乙酰化（H3ac）和组蛋白H3赖氨酸4三甲基化（H3K4me3）有关。使用染色质免疫沉淀（ChIP），我们检测了肌球蛋白重链（MHC）基因在快纤维型骨骼肌和慢纤维型骨骼肌中表达的组蛋白修饰，以及肌肉卸载模型，这导致慢肌肉中快速MHC基因表达的转变。在快纤维型植物和慢纤维型比目鱼中，H3ac和H3K4me3与MHC基因的转录活性直接相关。在肌肉卸载的MHC转变过程中，I型MHC的组蛋白H3随着该基因的下调而去乙酰化，而快速型IIx和IIb MHC的上调则与这些MHC中H3ac的增强一起发生。在IIx型和IIb型MHCs中，当这些基因被肌肉卸载诱导时，H3K4me3的富集也增加。然而，IIa MHC的下调与H3ac或H3K4me3的相应缺失无关。这些观察结果证明了使用ChIP分析来了解成人骨骼肌天然染色质环境的可行性，并且还表明I型、IIx型和IIb型MHC基因的转录状态对不同肌肉纤维类型和负载状态改变的组蛋白修饰都很敏感。
Pandorf CE, Haddad F, Wright C, Bodell PW, Baldwin KM. Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading. Am J Physiol Cell Physiol 297: C6-C16, 2009. First published April 15, 2009; doi:10.1152/ajpcell.00075.2009.-Recent advances in chromatin biology have enhanced our understanding of gene regulation. It is now widely appreciated that gene regulation is dependent upon post-translational modifications to the histones which package genes in the nucleus of cells. Active genes are known to be associated with acetylation of histones (H3ac) and trimethylation of lysine 4 in histone H3 (H3K4me3). Using chromatin immunoprecipitation (ChIP), we examined histone modifications at the myosin heavy chain (MHC) genes expressed in fast vs. slow fiber-type skeletal muscle, and in a model of muscle unloading, which results in a shift to fast MHC gene expression in slow muscles. Both H3ac and H3K4me3 varied directly with the transcriptional activity of the MHC genes in fast fiber-type plantaris and slow fiber-type soleus. During MHC transitions with muscle unloading, histone H3 at the type I MHC becomes de-acetylated in correspondence with downregulation of that gene, while upregulation of the fast type IIx and IIb MHCs occurs in conjunction with enhanced H3ac in those MHCs. Enrichment of H3K4me3 is also increased at the type IIx and IIb MHCs when these genes are induced with muscle unloading. Downregulation of IIa MHC, however, was not associated with corresponding loss of H3ac or H3K4me3. These observations demonstrate the feasibility of using the ChIP assay to understand the native chromatin environment in adult skeletal muscle, and also suggest that the transcriptional state of types I, IIx and IIb MHC genes are sensitive to histone modifications both in different muscle fiber-types and in response to altered loading states.