组蛋白酰基化修饰作用及其相关技术进展

Role of histone acylation and related technical developments

蛋白质翻译后修饰是细胞中调节蛋白质稳定性与生物活性的一种重要机制.近些年发现的多种新型的蛋白质翻译后修饰,特别是组蛋白的翻译后修饰,极大地扩展了人们对表观遗传学方式调控染色质结构和基因表达的认识.组蛋白作为与DNA结合的蛋白质,可以调控染色质的重塑,决定染色质局部的开放与关闭,可以在全基因组范围内控制基因的表达与否及表达水平,因而组蛋白的翻译后修饰非常重要.受细胞代谢调控的蛋白质酰基化修饰在组蛋白中引入酰基基团导致染色质构象改变引起基因表达和细胞表型的改变.探究酰基化修饰对染色质的动态影响的技术发展快、适用性强,近年来研究中常用ChIP-seq等技术检测组蛋白修饰与DNA序列的对应关系,用DNase-seq等技术研究不同染色质序列开放程度的改变,而如今出现的CUT&Tag与ATAC-seq分别代表两种实验的优化版本,它们又被改造用于单细胞实验、空间组学和多组学实验.生命科学是技术推动的领域,本文综述了研究组蛋白酰基化修饰的常用技术发展历程,并简要介绍了近年的新技术带来的实验发现.

Post-translational modifications of protein are improtant mechanisms that regulate protein stability or biological activity in cells.The discovery of various novel post-translational modifications of proteins,especially histones,has greatly expanded the understanding of epigenetic regulation of chromatin structure and gene expression.Histones,as proteins that bind to DNA,can regulate chromatin remodeling and determine the accessibility of chromatin,and control gene expression levels throughout the entire genome.Therefore,post-translational modifications of histones are very important.The acylation modification of proteins regulated by cellular metabolism introduces acyl groups into histones,leading to changes in chromatin conformation and changes in gene expression and cell phenotypes.The technology used to study how acylation modification affects chromatin has developed rapidly and has many applications.ChIP-seq is used to study DNA sequences binding with transcription factors,and methods like DNase-seq to study the accessibility changes of chromatin.Newly emerged CUT&Tag and ATAC-seq represent the improved versions of these two experimental methods,respectively,and they are further adapted to single-cell,spatial and multi-omics experiments.Given that techniques develop very rapid,this review summarized the recent progress of commonly used methods for histone acylation,and briefly described the new methods.