表观遗传与microRNA相互调控机制以及在抗肿瘤领域内的应用

DNA甲基化和组蛋白修饰等表观遗传机制是恶性肿瘤发生发展的重要原因之一．然而近年来研究发现,microRNA表达水平改变也参与恶性肿瘤的形成．最新研究资料揭示,表观遗传可调控microRNA表达,而一些种类的microRNA也可调节表观遗传,并且二者之间相互作用可调控组织细胞内基因表达以及诱导体内恶性肿瘤产生．研究资料还显示,表观遗传主要通过DNA甲基化、组蛋白修饰等方式调控microRNA表达,而microRNA则通过调节DNA甲基化转移酶、维持细胞中DNA甲基化水平或改变组蛋白修饰等途径调控表观遗传．对microRNA与表观遗传之间的调控关系以及在抗肿瘤领域内的应用进行全面而系统的论述．     

DNA甲基化与基因表达调控研究进展

表观遗传修饰是指不改变DNA序列的、可遗传的对碱基和组蛋白的化学修饰,主要包括DNA甲基化、组蛋白修饰、染色质重塑以及非编码RNA等.表观遗传修饰是更高层次的基因表达调控手段.DNA甲基化是一种重要的表观遗传修饰,参与基因表达调控、基因印记、转座子沉默、X染色体失活以及癌症发生等重要生物学过程.近年来随着研究方法和技术的进步,全基因组DNA甲基化的研究广泛兴起,多个物种全基因组甲基化图谱被破译,全局水平对DNA甲基化的研究不仅利于在宏观层面上了解DNA甲基化的特性与规律,同时也为深入分析DNA甲基化的生物学功能与调控奠定了基础.结合最新研究进展综述DNA甲基化在基因组中的分布模式、规律以及和基因转录的关系等.     

表观遗传调控在糖尿病及其并发症中的作用

表观遗传(epigenetics)是指DNA序列不发生变化但基因表达却发生了可遗传的改变．表观遗传调控过程十分复杂,主要包括DNA甲基化、组蛋白修饰和微小RNA(miRNA)等．糖尿病是一种慢性代谢性疾病,常伴随大血管和微血管并发症．糖尿病的发生、发展不仅取决于遗传因素,而且也受到表观遗传修饰的调控．因此,对表观遗传调控的研究将为糖尿病及其并发症的预防和治疗提供新的思路和方法．     

运动对骨骼肌基因表达的表观遗传调控作用

DNA甲基化、组蛋白修饰和miRNA表达调控是表观遗传调控的3种重要方式,其在基因表达调控中发挥着关键作用。适当运动有益于身心健康。骨骼肌作为运动的主体组织,运动可以提高其代谢能力,改善其线粒体生物学功能,调控肌纤维类型转化,增加骨骼肌力量。近年来越来越多的研究表明,表观遗传调控在机体适应运动过程中发挥着重要作用,DNA甲基化、组蛋白修饰和miRNA表达调控等表观遗传调控方式通过调控骨骼肌基因表达来改变骨骼肌代谢能力、线粒体生物学功能和肌纤维类型,从而适应运动变化。本文对近年来运动对骨骼肌基因DNA甲基化、组蛋白修饰和相应miRNA表达调控等3种表观遗传调控方式的研究现状进行了综述,以期为进一步研究运动改善机体机能和健康提供参考。     

植物中表观遗传修饰研究进展

表观遗传是指DNA序列不发生变化, 但基因表达发生了可遗传的改变, 主要涉及DNA与染色体上的一些可逆修饰以及一些转录调控机制。DNA甲基化、组蛋白修饰和非编码RNA调控是表观遗传学研究的三大支柱。三者在植物生长发育、应对生物和非生物胁迫以及适应环境变化中发挥着极其重要的作用。该文综述了植物中DNA甲基化、组蛋白修饰、非编码RNA调控的研究进展及其对植物株高、生育期、花型、果实着色以及应对环境胁迫等方面的影响。     

表观遗传修饰在调控寿命中的作用

表观遗传修饰是生命现象中普遍存在的一类基因调控方式,主要包括DNA甲基化、组蛋白乙酰化和组蛋白甲基化等,通常协同调控基因表达。端粒是位于真核生物染色体末端的保护性结构,在端粒以及亚端粒区域中也存在丰富的表观遗传修饰。随着研究深入,发现表观遗传修饰在调控寿命过程中扮演着重要角色,而揭示衰老的有关机制有助于我们找到延长寿命的方法,具有重大的生物学意义和临床应用前景。     

表观遗传修饰对肝纤维化调控作用的研究进展

肝纤维化(hepatic fibrosis, HF)是由各种致病因子所引起的肝脏持续炎症反应和纤维结缔组织异常增生的过程,是肝硬化和肝癌发展的必经阶段。近年来,越来越多的研究发现表观遗传修饰通过改变DNA甲基化、组蛋白修饰及非编码RNA (non-coding RNA, ncRNA)表达等,在不改变核酸序列的前提下,对肝内实质细胞和非实质细胞的重要信号转导通路、细胞因子和趋化因子的表达等进行调控,进而影响肝纤维化的发生发展。该文就表观遗传修饰在肝纤维化中的调控作用进行综述。     

水稻/拟南芥防御病原细菌入侵的表观遗传调控研究进展

表观遗传修饰是指在不改变基因序列的情况下,通过对DNA和组蛋白等一系列可逆的共价修饰调控生物体的基因表达,在应对生物和非生物因素胁迫以及适应环境变化的过程中发挥着非常重要的作用。最近的研究表明,表观遗传修饰参与水稻/拟南芥抵御细菌入侵的免疫反应(包括效应识别、信号转导和快速防御反应等)。对基因组DNA甲基化、组蛋白修饰(甲基化/去甲基化、乙酰化/去乙酰化和泛素化)和小RNA在内的表观遗传修饰在水稻/拟南芥对病原细菌入侵的防御反应中的功能和分子调控机制进行了综述,有助于系统地全面理解表观遗传抗病性,为其抗病育种提供理论支持和基因资源。     

表观遗传修饰在糖脂代谢中的作用

表观遗传学是研究没有DNA序列变化的、可遗传的基因表达改变。表观遗传修饰可以参与多种生命过程,其在糖脂代谢中也发挥了重要的作用。生物体内的糖脂代谢关系密切,糖脂代谢紊乱会导致多种代谢性疾病的发生。文章主要从DNA甲基化、组蛋白修饰、非编码RNA调控等方面综述了表观遗传修饰在糖脂代谢中的研究进展。     

黑色素瘤发生发展中的表观遗传学调控

人恶性黑色素瘤(malignant melanoma)是近年来高发病率和高死亡率的肿瘤之一.目前尚缺乏有效的治疗方法.而表观遗传如DNA甲基化(DNA methylation)、组蛋白修饰(histonemodification)、染色质重塑(chromatin remodeling)及RNA干扰(RNA interference,RNAi)等改变在人黑色素瘤的发生、发展和转移中有重要作用.阐明黑色素瘤发生发展的表观遗传学机制已引起了学者的普遍关注.本文综述了人类黑色素瘤发生发展中所特异的表观遗传改变:CpG岛的异常甲基化修饰、组蛋白甲基化和乙酰化修饰、染色质重塑以及microRNA在黑色素瘤发生和转移中的作用,并对应用表观遗传修饰治疗人类黑色素瘤进行了探讨.     

Epigenetics in Ocular Diseases

Epigenetics pertains to heritable alterations in gene expression that do not involve modification of the underlying genomic DNA sequence. Historically, the study of epigenetic mechanisms has focused on DNA methylation and histone modifications, but the concept of epigenetics has been more recently extended to include microRNAs as well. Epigenetic patterning is modified by environmental exposures and may be a mechanistic link between environmental risk factors and the development of disease. Epigenetic dysregulation has been associated with a variety of human diseases, including cancer, neurological disorders, and autoimmune diseases. In this review, we consider the role of epigenetics in common ocular diseases, with a particular focus on DNA methylation and microRNAs. DNA methylation is a critical regulator of gene expression in the eye and is necessary for the proper development and postmitotic survival of retinal neurons. Aberrant methylation patterns have been associated with age-related macular degeneration, susceptibility to oxidative stress, cataract, pterygium, and retinoblastoma. Changes in histone modifications have also been observed in experimental models of diabetic retinopathy and glaucoma. The expression levels of specific microRNAs have also been found to be altered in the context of ocular inflammation, retinal degeneration, pathological angiogenesis, diabetic retinopathy, and ocular neoplasms. Although the complete spectrum of epigenetic modifications remains to be more fully explored, it is clear that epigenetic dysregulation is an important contributor to common ocular diseases and may be a relevant therapeutic target.     

酵母模式生物研究表观遗传调控基因组稳定性的进展

基因组的遗传稳定性是维持正常的细胞复制、增殖和分化的关键。外源因素和内源因素造成的DNA损伤及其修复失败, 是各种遗传疾病发生的根本原因。表观遗传调控(包括DNA甲基化、组蛋白修饰和非编码RNA)在DNA损伤修复和细胞周期调控方面发挥着重要的作用, 也是维持基因组稳定性的基础。酵母作为单细胞真核生物, 是最早开展表观遗传学研究的物种之一, 特别是在DNA损伤修复和异染色质形成等方面的研究, 为揭示遗传稳定性的本质提供了理论依据。国际上前期以酵母为模式生物研究表观遗传学的报道主要集中于组蛋白修饰领域; 近期利用裂殖酵母作为模式生物研究RNAi指导的组蛋白修饰也有了一定的进展。文章以酵母作为模式生物, 论述了表观遗传修饰在维持基因组遗传稳定性中的研究进展、作用机制和今后的发展趋势。     

表观遗传学: 生物细胞非编码RNA调控的研究进展

表观遗传学是研究基因表达发生了可遗传的改变, 而DNA序列不发生改变的一门生物学分支, 对细胞的生长分化及肿瘤的发生发展至关重要。表观遗传学的主要机制包括DNA甲基化、组蛋白修饰及新近发现的非编码RNA。非编码RNA 是指不能翻译为蛋白的功能性RNA分子, 其中常见的具调控作用的非编码RNA包括小干涉RNA、miRNA、piRNA 以及长链非编码RNA。近年来大量研究表明非编码RNA在表观遗传学的调控中扮演了越来越重要的角色。文章综述了近年来生物细胞非编码RNA调控的表观遗传学研究进展, 以有助于理解哺乳动物细胞中非编码RNA及其调控机制和功能。     

植物表观遗传修饰与病原菌胁迫应答研究进展

真核生物基因表达受到染色质结构的调控,组蛋白与DNA的共价修饰构成表观遗传标签,并在植物胁迫应答如防御病原菌侵染过程中起重要作用.病原菌侵染可引起基因组整体DNA甲基化模式变化及胁迫应答基因的位点特异性去甲基化,导致植物抗性基因表达上调或下调,并进一步调控植物对病原菌的胁迫应答;组蛋白去乙酰化酶HDAC通过茉莉酸途径增强植物对病原菌的胁迫应答;此外,染色质重塑复合物Swr1复合体通过识别DNA基元和组蛋白乙酰化修饰状态靶向基因启动子,负调控SA敏感基因.该文从DNA甲基化、组蛋白乙酰化、甲基化修饰,染色质重塑等方面着重阐述植物与病原菌互作过程中发生的主要事件的分子基础及其研究进展.     

Advances in chromatin remodeling and human disease

Epigenetic factors alter phenotype without changing genotype. A primary molecular mechanism underlying epigenetics is the alteration of chromatin structure by covalent DNA modifications, covalent histone modifications, and nucleosome reorganization. Remodeling of chromatin structure regulates DNA methylation, replication, recombination, and repair as well as gene expression. As these functions would predict, dysfunction of the proteins that remodel chromatin causes an array of multi-system disorders and neoplasias. Insights from these diseases suggest that during embryonic and fetal life, environmental distortions of chromatin remodeling encode a 'molecular memory' that predispose the individual to diseases in adulthood.     

Crosstalk Between DNA and Histones: Tet’s New Role in Embryonic Stem Cells

Embryonic stem (ES) cells are characterized by the expression of an extensive and interconnected network of pluripotency factors which are downregulated in specialized cells. Epigenetic mechanisms, including DNA methylation and histone modifications, are also important in maintaining this pluripotency program in ES cells and in guiding correct differentiation of the developing embryo. Methylation of the cytosine base of DNA blocks gene expression in all cell types and further modifications of methylated cytosine have recently been discovered. These new modifications, putative intermediates in a pathway to erase DNA methylation marks, are catalyzed by the ten-eleven translocation (Tet) proteins, specifically by Tet1 and Tet2 in ES cells. Surprisingly, Tet1 shows repressive along with active effects on gene expression depending on its distribution throughout the genome and co-localization with Polycomb Repressive Complex 2 (PRC2). PRC2 di- and tri-methylates lysine 27 of histone 3 (H3K27me2/3 activity), marking genes for repression. In ES cells, almost all gene loci containing the repressive H3K27me3 modification also bear the active H3K4me3 modification, creating “bivalent domains” which mark important developmental regulators for timely activation. Incorporation of Tet1 into the bivalent domain paradigm is a new and exciting development in the epigenetics field, and the ramifications of this novel crosstalk between DNA and histone modifications need to be further investigated. This knowledge would aid reprogramming of specialized cells back into pluripotent stem cells and advance understanding of epigenetic perturbations in cancer.     

Epigenetic modifications of histones during osteoblast differentiation

In bone biology, epigenetics plays a key role in mesenchymal stem cells' (MSCs) commitment towards osteoblasts. It involves gene regulatory mechanisms governed by chromatin modulators. Predominant epigenetic mechanisms for efficient osteogenic differentiation include DNA methylation, histone modifications, and non-coding RNAs. Among these mechanisms, histone modifications critically contribute to altering chromatin configuration. Histone based epigenetic mechanisms are an essential mediator of gene expression during osteoblast differentiation as it directs the bivalency of the genome. Investigating the importance of histone modifications in osteogenesis may lead to the development of epigenetic-based remedies for genetic disorders of bone. Hence, in this review, we have highlighted the importance of epigenetic modifications such as post-translational modifications of histones, including methylation, acetylation, phosphorylation, ubiquitination, and their role in the activation or suppression of gene expression during osteoblast differentiation. Further, we have emphasized the future advancements in the field of epigenetics towards orthopaedical therapeutics.     

Epigenetics and cell cycle regulation in cystogenesis

The role of genetic mutations in the development of polycystic kidney disease (PKD), such as alterations in PKD1 and PKD2 genes in autosomal dominant PKD (ADPKD), is well understood. However, the significance of epigenetic mechanisms in the progression of PKD remains unclear and is increasingly being investigated. The term of epigenetics describes a range of mechanisms in genome function that do not solely result from the DNA sequence itself. Epigenetic information can be inherited during mammalian cell division to sustain phenotype specifically and physiologically responsive gene expression in the progeny cells. A multitude of functional studies of epigenetic modifiers and systematic genome-wide mapping of epigenetic marks reveal the importance of epigenomic mechanisms, including DNA methylation, histone/chromatin modifications and non-coding RNAs, in PKD pathologies. Deregulated proliferation is a characteristic feature of cystic renal epithelial cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cyst formation and progression. Recent evidence suggests that alterations of DNA methylation and histone modifications on specific genes and the whole genome involved in cell cycle regulation and contribute to the pathogenesis of PKD. This review summarizes the recent advances of epigenetic mechanisms in PKD, which helps us to define the term of “PKD epigenetics” and group PKD epigenetic changes in three categories. In particularly, this review focuses on the interplay of epigenetic mechanisms with cell cycle regulation during normal cell cycle progression and cystic cell proliferation, and discusses the potential to detect and quantify DNA methylation from body fluids as diagnostic/prognostic biomarkers. Collectively, this review provides concepts and examples of epigenetics in cell cycle regulation to reveal a broad view of different aspects of epigenetics in biology and PKD, which may facilitate to identify possible novel therapeutic intervention points and to explore epigenetic biomarkers in PKD.