The interplay of histone modifications - writers that read.
The interplay of histone modifications - writers that read.
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DOI：
10.15252/embr.201540945
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发表时间：
2015-11
期刊：
影响因子：
7.7
通讯作者：
Brockdorff N
中科院分区：
文献类型：
--
作者：
Zhang T;Cooper S;Brockdorff N
组蛋白受到大量翻译后修饰，包括乙酰化、甲基化、磷酸化和泛素化。这些修饰的作者在正常发育中发挥着重要作用，它们的突变或失调与遗传性疾病和各种癌症有关。这些标记的阅读器包含允许其招募到染色质的蛋白质结构域。有趣的是，作者通常包含可以读取染色质标记的域，从而允许通过正反馈循环强化修饰或通过其他修饰抑制其活性。我们讨论了这种积极的强化如何导致染色质状态稳定，并且可以通过细胞分裂进行表观遗传维持。我们描述了这些调控系统与修饰相关的影响，包括与活性基因相关的 H3K4me3、H3K79me3 和 H3K36me3 以及与转录抑制相关的 H3K27me3 和 H3K9me3。我们还回顾了主动修饰和抑制修饰之间的串扰，通过 Polycomb 和 Trithorax 组蛋白修饰蛋白之间的相互作用来说明，并讨论这对于定义发育过程中的基因表达状态如何重要。
Histones are subject to a vast array of posttranslational modifications including acetylation, methylation, phosphorylation, and ubiquitylation. The writers of these modifications play important roles in normal development and their mutation or misregulation is linked with both genetic disorders and various cancers. Readers of these marks contain protein domains that allow their recruitment to chromatin. Interestingly, writers often contain domains which can read chromatin marks, allowing the reinforcement of modifications through a positive feedback loop or inhibition of their activity by other modifications. We discuss how such positive reinforcement can result in chromatin states that are robust and can be epigenetically maintained through cell division. We describe the implications of these regulatory systems in relation to modifications including H3K4me3, H3K79me3, and H3K36me3 that are associated with active genes and H3K27me3 and H3K9me3 that have been linked to transcriptional repression. We also review the crosstalk between active and repressive modifications, illustrated by the interplay between the Polycomb and Trithorax histone-modifying proteins, and discuss how this may be important in defining gene expression states during development.