Oxidative stress-mediated alterations in histone post-translational modifications
Oxidative stress-mediated alterations in histone post-translational modifications
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DOI：
10.1016/j.freeradbiomed.2021.02.027
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发表时间：
2021-06-16
影响因子：
7.4
通讯作者：
Pallardo，Federico
中科院分区：
文献类型：
--
作者：
Garcia-Gimenez，Jose-Luis;Garces，Concepcion;Pallardo，Federico
基因表达的表观遗传调控为细胞在经历环境变化时提供了微调的反应能力。然而，在人类生理学或疾病的背景下，任何调节动态平衡的细胞失衡都有可能触发分子变化，导致对新情况或病理条件的生理适应。这些影响的部分原因是表观遗传调节功能的改变，这会导致细胞谱系的长期且往往是可遗传的变化。因此，不平衡/延长的氧化应激所产生的自由基已被证明是表观遗传剂的调节器，导致表观遗传格局的改变。在这篇综述中，我们将集中于氧化应激和自由基在组蛋白翻译后修饰中产生的特殊影响，这些修饰有助于改变组蛋白编码，从而改变基因表达。基因表达的这种表观遗传层的变化的病理后果，从许多生理适应过程中收集的数据和人类疾病中收集的数据，从年龄相关的神经退行性病理到癌症，包括呼吸综合征、不孕不育和全身炎症状况(如败血症)，都充分证明了这一点。
Epigenetic regulation of gene expression provides a finely tuned response capacity for cells when undergoing environmental changes. However, in the context of human physiology or disease, any cellular imbalance that modulates homeostasis has the potential to trigger molecular changes that result either in physiological adaptation to a new situation or pathological conditions. These effects are partly due to alterations in the functionality of epigenetic regulators, which cause long-term and often heritable changes in cell lineages. As such, free radicals resulting from unbalanced/extended oxidative stress have been proved to act as modulators of epigenetic agents, resulting in alterations of the epigenetic landscape. In the present review we will focus on the particular effect that oxidative stress and free radicals produce in histone post-translational modifications that contribute to altering the histone code and, consequently, gene expression. The pathological consequences of the changes in this epigenetic layer of regulation of gene expression are thoroughly evidenced by data gathered in many physiological adaptive processes and in human diseases that range from age-related neurodegenerative pathologies to cancer, and that include respiratory syndromes, infertility, and systemic inflammatory conditions like sepsis.