组蛋白精氨酸甲基化修饰对基因转录的调控

总结了组蛋白精氨酸甲基化修饰体系的最新研究进展．组蛋白精氨酸甲基化修饰在基因转录调控中发挥着十分重要的作用,这类修饰由蛋白精氨酸甲基转移酶（PRMTs）介导,其中PRMT1和PRMT4的甲基化修饰与基因的转录激活作用相关,PRMT5和PRMT6的甲基化修饰则与基因的转录抑制作用相关．组蛋白精氨酸的甲基化是一个动态的可逆过程,催化组蛋白精氨酸的去甲基化是由“精氨酸去甲基化酶”介导的．     

组蛋白共价修饰——组蛋白H3第4赖氨酸甲基化

染色体组蛋白的共价修饰在调节染色体结构,控制基因的转录等方面发挥重要的作用。组蛋白H3第4赖氨酸的甲基化作为共价修饰的方式之一,可以调控基因的转录激活。随着对组蛋白甲基化转移酶及相关作用蛋白研究的深入,人们对组蛋白H3第4赖氨酸的甲基化的功能也有了更深的了解。目前研究发现它与癌症也有很密切的关系。     

真菌组蛋白赖氨酸甲基转移酶的研究进展

甲基化修饰是蛋白翻译后修饰的主要方式之一。真菌中,多种赖氨酸甲基转移酶能够执行组蛋白特定位点上赖氨酸的甲基化。组蛋白上赖氨酸的甲基化与真菌DNA的复制、转录以及异染色质的形成相关。甲基化参与了多种生物学过程,如真菌发育、昼夜节律调节、次级代谢基因簇表达、水解酶合成、致病真菌毒力形成。本文结合笔者工作,对目前真菌中已经发现的组蛋白赖氨酸甲基转移酶的命名、分类、结构域特征、催化域的三维结构以及它们所执行的甲基化在各种真菌中的作用进行了总结,提出了目前研究的不足并对未来的研究方向和内容进行了展望。     

组蛋白H3K36甲基化与疾病

组蛋白H3K36位点可以发生甲基化修饰,其修饰状态受到H3K36甲基转移酶和去甲基化酶的动态调控。H3K36的甲基化修饰可引起多种生物学效应,如参与基因的转录激活或抑制、剂量补偿以及基因的选择性剪接等。H3K36甲基化修饰状态的异常与很多疾病相关,因此全面了解H3K36甲基化对于该类疾病的诊断和治疗具有重要意义。     

组蛋白甲基化的研究进展

组蛋白甲基化是细胞中一种普遍而重要的表观遗传修饰方式,由组蛋白甲基转移酶完成.对组蛋白甲基化修饰认识已有相当长的时间,但直到最近几年由于组蛋白甲基化修饰酶的发现才使人们逐渐认识到组蛋白甲基化修饰有广泛的生物学功能.本文拟从组蛋白甲基转移酶、组蛋白甲基化的功能以及组蛋白甲基化与DNA甲基化的关系等方面综述这一领域的研究进展.     

组蛋白甲基化修饰效应分子的研究进展

作为一种重要的表观遗传学调控机制,组蛋白甲基化修饰在多种生命过程中发挥了重要的作用。细胞内有多种组蛋白甲基化酶和去甲基化酶共同调节组蛋白的修饰状态,在组蛋白甲基化状态确定后,多种效应分子特异的读取修饰信息,从而参与基因转录调控过程。文章从组蛋白甲基化效应分子的作用机制方面综述了这一领域的研究进展。     

组蛋白甲基化研究进展

组蛋白甲基化是表观遗传修饰方式中的一种,参与异染色质形成、基因印记、X染色体失活和基因转录调控.组蛋白甲基化过程的异常参与多种肿瘤的发生.既往认为组蛋白甲基化是稳定的表观遗传标记,而组蛋白去甲基化酶的发现对这一观点提出了挑战,也为进一步深入研究组蛋白修饰提供新的途径.     

基因组DNA甲基化修饰在胚胎干细胞分化过程中的作用

基因组DNA的甲基化修饰通常使基因转录失活,去甲基化或低甲基化则使基因转录活化。但是,胚胎干细胞向各种成体细胞分化过程中相关基因的转录活化与DNA甲基化修饰水平并不呈简单的正性或负性相关。因此,甲基化修饰调节基因转录是一个复杂的过程。目前,对甲基化修饰作用的研究主要集中在基因选择性活化、改变转录因子与靶基因的结合活性、与组蛋白修饰协同作用及其基因表达的阶段特异性等方面。     

组蛋白甲基化及其与肿瘤间的关系

组蛋白甲基化修饰是表观遗传学的重要研究领域之一,主要可分为精氨酸甲基化和赖氨酸甲基化两种。越来越多的证据表明组蛋白甲基化功能异常与肿瘤的发生发展密切相关,而且这种甲基化修饰过程是可逆的。对组蛋白甲基化的进一步研究,不仅有助于深入了解基因表达、调控、遗传等生理机制,而且对于肿瘤等重大疾病的诊断、防治和预后判断有重要意义。本文对组蛋白甲基转移酶、去甲基化酶及其与肿瘤发生发展的关系予以综述。     

组蛋白去甲基化酶在发育和再生医学的研究

表观遗传学调控在器官发育以及再生医学中是重要的研究内容,而组蛋白的甲基化修饰属于表观遗传学调控机制之一并且成为近年来研究的热点内容。处于不同甲基化状态下的组蛋白,能影响多种分子对其的识别和结合,在转录起始、转录效率和转录后加工等多个层面调控相关基因的表达。而哺乳动物的器官发育与细胞重编程都与基因选择性表达密切相关,因此组蛋白甲基化状态在基因选择性表达中扮演着重要角色。本文概述了组蛋白去甲基化酶的分类以及组蛋白不同甲基化状态下对于基因的表达的调控,同时总结了组蛋白去甲基化酶在维持胚胎干细胞的多分化潜能和IPS细胞重编程效率方面的作用以及组蛋白去甲基化酶基因的缺失与相关器官发育的影响。最后探讨了组蛋白甲基化修饰酶在推动发育生物学与再生医学研究进展方面的潜能。     

On your histone mark,SET, methylate!

Lysine methylation of histones and non-histone proteins has emerged in recent years as a posttranslational modification with wide-ranging cellular implications beyond epigenetic regulation. The molecular interactions between lysine methyltransferases and their substrates appear to be regulated by posttranslational modifications surrounding the lysine methyl acceptor. Two very interesting examples of this cross-talk between methyl-lysine sites are found in the SET (Su(var)3–9, Enhancer-of-zeste, Trithorax) domain-containing lysine methyltransferases SET7 and SETDB1, whereby the histone H3 trimethylated on lysine 4 (H3K4^me3) modification prevents methylation by SETDB1 on H3 lysine 9 (H3K9) and the histone H3 trimethylated on lysine 9 (H3K9^me3) modification prevents methylation by SET7 on H3K4. A similar cross-talk between posttranslational modifications regulates the functions of non-histone proteins such as the tumor suppressor p53 and the DNA methyltransferase DNMT1. Herein, in cis effects of acetylation, phosphorylation, as well as arginine and lysine methylation on lysine methylation events will be discussed.     

The function of histone lysine methylation related SET domain group proteins in plants

Histone methylation, which is mediated by the histone lysine (K) methyltransferases (HKMTases), is a mechanism associated with many pathways in eukaryotes. Most HKMTases have a conserved SET (Su(var) 3‐9,E(z),Trithorax) domain, while the HKMTases with SET domains are called the SET domain group (SDG) proteins. In plants, only SDG proteins can work as HKMTases. In this review, we introduced the classification of SDG family proteins in plants and the structural characteristics of each subfamily, surmise the functions of SDG family members in plant growth and development processes, including pollen and female gametophyte development, flowering, plant morphology and the responses to stresses. This review will help researchers better understand the SDG proteins and histone methylation in plants and lay a basic foundation for further studies on SDG proteins.     

Three-dimensional structures of fibrillar Sm proteins: Hfq and other Sm-like proteins

SET domain lysine methyltransferases are known to catalyze site and state-specific methylation of lysine residues in histones that is fundamental in epigenetic regulation of gene activation and silencing in eukaryotic organisms. Here we report the three-dimensional solution structure of the SET domain histone lysine methyltransferase (vSET) from Paramecium bursaria chlorella virus 1 bound to cofactor S-adenosyl-L-homocysteine and a histone H3 peptide containing mono-methylated lysine 27. The dimeric structure, mimicking an enzyme/cofactor/substrate complex, yields the structural basis of the substrate specificity and methylation multiplicity of the enzyme. Our results from mutagenesis and enzyme kinetics analyses argue that a general base mechanism is less likely for lysine methylation by SET domains; and that the only invariant active site residue tyrosine 105 in vSET facilitates methyl transfer from cofactor to the substrate lysine by aligning intermolecular interactions in the lysine access channel of the enzyme.     

Dynamics of epigenetic control in plants via SET domain containing proteins: Structural and functional insights

Plants control expression of their genes in a way that involves manipulating the chromatin structural dynamics in order to adapt to environmental changes and carry out developmental processes. Histone modifications like histone methylation are significant epigenetic marks which profoundly and globally modify chromatin, potentially affecting the expression of several genes. Methylation of histones is catalyzed by histone lysine methyltransferases (HKMTs), that features an evolutionary conserved domain known as SET [Su(var)3–9, E(Z), Trithorax]. This methylation is directed at particular lysine (K) residues on H3 or H4 histone. Plant SET domain group (SDG) proteins are categorized into different classes that have been conserved through evolution, and each class have specificity that influences how the chromatin structure operates. The domains discovered in plant SET domain proteins have typically been linked to protein-protein interactions, suggesting that majority of the SDGs function in complexes. Additionally, SDG-mediated histone mark deposition also affects alternative splicing events. In present review, we discussed the diversity of SDGs in plants including their structural properties. Additionally, we have provided comprehensive summary of the functions of the SDG-domain containing proteins in plant developmental processes and response to environmental stimuli have also been highlighted.     

DOT1—— 一类新的组蛋白赖氨酸甲基转移酶

组蛋白甲基化是一种重要的组蛋白共价修饰, 在染色质结构和基因表达的调控过程中起着重要的、多样化的作用。DOT1催化核心球体部位的组蛋白H3第79位赖氨酸(H3K79)使其发生甲基化, 是首个被发现的无SET结构域的组蛋白赖氨酸甲基转移酶, 代表了一类新的组蛋白赖氨酸甲基转移酶。DOT1及H3K79甲基化的特点决定了其可能具有重要的、特殊的生物学功能。文章重点综述了DOT1蛋白的结构及特点, DOT1及H3K79甲基化的生物学功能以及组蛋白泛素化修饰对H3K79甲基化的反式调控。