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与其靶点相关的乙酰化和甲基化相关表观遗传蛋白

Acetylation- and Methylation-Related Epigenetic Proteins in the Context of Their Targets.

作者信息

Javaid Nasir, Choi Sangdun

机构信息

Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.

出版信息

Genes (Basel). 2017 Aug 7;8(8):196. doi: 10.3390/genes8080196.

Abstract

The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed "epigenetics". These modifications play critical roles, either by affecting non-histone protein recruitment to chromatin or by disturbing chromatin contacts. Their presence dictates the condensed packaging of DNA and can coordinate the orderly recruitment of various enzyme complexes for DNA manipulation. This genetic modification machinery involves various writers, readers, and erasers that have unique structures, functions, and modes of action. Regarding human disease, studies have mainly focused on the genetic mechanisms; however, alteration in the balance of epigenetic networks can result in major pathologies including mental retardation, chromosome instability syndromes, and various types of cancers. Owing to its critical influence, great potential lies in developing epigenetic therapies. In this regard, this review has highlighted mechanistic and structural interactions of the main epigenetic families with their targets, which will help to identify more efficient and safe drugs against several diseases.

摘要

核小体表面覆盖着多种修饰,这些修饰由八类不同的酶维持。这些酶修饰DNA和组蛋白上的特定靶位点,这些修饰已得到充分鉴定并被称为“表观遗传学”。这些修饰发挥着关键作用,要么通过影响非组蛋白招募至染色质,要么通过扰乱染色质接触。它们的存在决定了DNA的浓缩包装,并能协调各种酶复合物有序招募以进行DNA操作。这种基因修饰机制涉及各种“书写者”“阅读者”和“擦除者”,它们具有独特的结构、功能和作用方式。关于人类疾病,研究主要集中在遗传机制;然而,表观遗传网络平衡的改变可导致包括智力迟钝、染色体不稳定综合征和各种癌症在内的主要病理学改变。由于其关键影响,开发表观遗传疗法具有巨大潜力。在这方面,本综述强调了主要表观遗传家族与其靶标的机制和结构相互作用,这将有助于识别针对多种疾病更高效、更安全的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd7e/5575660/fc086acf510b/genes-08-00196-g001.jpg

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