擦除错误:组蛋白赖氨酸甲基化去除与疾病之间的联系

Elizabeth M Duncan, C David Allis
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引用次数: 24

摘要

许多研究表明,共价组蛋白修饰是动态调节的,可以引起染色质模板的化学和物理变化。染色质模板的这种变化导致生物学上显著的后果,包括差异基因表达。特别是,组蛋白赖氨酸甲基化已被证明与基因表达呈正相关或负相关,这取决于组蛋白序列中甲基化的特定位点和程度(即单-、二-或三-)。虽然建立或“书写”甲基修饰的蛋白质的遗传改变及其在各种人类疾病中的影响已经被记录在案,但最近才出现了去除或“抹去”组蛋白甲基化的蛋白质的错误调节与疾病之间的联系。在这里,我们讨论了三种机制,通过组蛋白甲基化可以从染色质模板中去除。我们描述了这些“擦除”机制如何与已知在疾病(如癌症)中被错误调节的途径相关联。我们进一步描述了组蛋白甲基化去除中的错误如何能够并且确实直接或间接地导致人类病理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Errors in erasure: links between histone lysine methylation removal and disease.

Many studies have demonstrated that covalent histone modifications are dynamically regulated to cause both chemical and physical changes to the chromatin template. Such changes in the chromatin template lead to biologically significant consequences, including differential gene expression. Histone lysine methylation, in particular, has been shown to correlate with gene expression both positively and negatively, depending on the specific site and degree (i.e., mono-, di-, or tri-) of methylation within the histone sequence. Although genetic alterations in the proteins that establish, or "write," methyl modifications and their effect in various human pathologies have been documented, connections between the misregulation of proteins that remove, or "erase," histone methylation and disease have emerged more recently. Here we discuss three mechanisms through which histone methylation can be removed from the chromatin template. We describe how these "erasure" mechanisms are linked to pathways that are known to be misregulated in diseases, such as cancer. We further describe how errors in the removal of histone methylation can and do lead to human pathologies, both directly and indirectly.

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