Metabolic Research Unit, School of Medicine, Deakin University, Waurn Ponds, Australia.
J Appl Physiol (1985). 2011 Jan;110(1):258-63. doi: 10.1152/japplphysiol.00979.2010. Epub 2010 Oct 28.
The spatial association between genomic DNA and histone proteins within chromatin plays a key role in the regulation of gene expression and is largely governed by post-translational modifications to histone proteins, particularly H3 and H4. These modifications include phosphorylation, acetylation, and mono-, di-, and tri-methylation, and while some are associated with transcriptional repression, acetylation of lysine residues within H3 generally correlates with transcriptional activation. Histone acetylation is regulated by the balance between the activities of histone acetyl transferase (HAT) and histone deacetylase (HDAC). In skeletal muscle, the class II HDACs 4, 5, 7, and 9 play a key role in muscle development and adaptation and have been implicated in exercise adaptations. As just one example, exercise results in the nuclear export of HDACs 4 and 5, secondary to their phosphorylation by CaMKII and AMPK, two kinases that are activated during exercise in response to changes in sarcoplasmic Ca(2+) levels and energy status, in association with increased GLUT4 expression in human skeletal muscle. Unraveling the complexities of the so-called "histone code" before and after exercise is likely to lead to a greater understanding of the regulation of exercise/activity-induced alterations in skeletal muscle gene expression and reinforce the importance of skeletal muscle plasticity in health and disease.
染色质中基因组 DNA 与组蛋白之间的空间关联在基因表达调控中起着关键作用，主要受组蛋白，特别是 H3 和 H4 的翻译后修饰调控。这些修饰包括磷酸化、乙酰化以及单、二和三甲基化，虽然有些与转录抑制有关，但 H3 赖氨酸残基的乙酰化通常与转录激活相关。组蛋白乙酰化受组蛋白乙酰转移酶（HAT）和组蛋白去乙酰化酶（HDAC）活性之间的平衡调节。在骨骼肌中，II 类 HDACs（4、5、7 和 9）在肌肉发育和适应中起着关键作用，并与运动适应有关。仅举一个例子，运动导致 HDACs 4 和 5 的核输出，这是由于它们被 CaMKII 和 AMPK 磷酸化的结果，这两种激酶在运动时会因肌浆 Ca（2+）水平和能量状态的变化而被激活，与人类骨骼肌中 GLUT4 表达增加有关。在运动前后揭示所谓的“组蛋白密码”的复杂性，可能会更深入地了解运动/活动引起的骨骼肌基因表达变化的调控，并强调骨骼肌可塑性在健康和疾病中的重要性。
