槲皮素健康效应的表观遗传学机制研究进展

表观遗传学是指在基因的核苷酸序列不发生改变的情况下,基因表达发生了可遗传性的改变,主要涉及DNA甲基化、组蛋白修饰及非编码RNA异常表达等,在生物生长、发育和疾病发生中发挥着重要的调节作用。槲皮素是一种天然的植物化学物,能通过表观遗传学的相关机制来调控基因的表达。文章总结了槲皮素参与基因甲基化、组蛋白修饰及microRNA异常表达等方面的研究进展,从表观遗传学调控的角度,综述了槲皮素发挥作用的新途径。     

辅助生殖技术与印迹基因失调性疾病相关性的研究进展

辅助生殖技术(ART)是治疗不孕不育症的有效手段,其生殖遗传安全性也一直备受关注。ART子代不良妊娠结局如低出生体质量儿、自然流产、胎儿畸形、早产、围生期死亡等的发生率不断增加,大量研究显示不孕不育患者通过控制性超促排卵、体外受精、胚胎操作等非生理性的干预对表观遗传造成一定的影响;表观遗传修饰中印迹基因对胎儿的发育具有重要的作用,ART实施于表观遗传重编程的关键时期,印迹基因的失调不仅影响胚胎的发育,还可诱发子代出生后的发育异常而导致多种相关性疾病的发生。本文从表观遗传修饰与印迹基因、ART与印迹基因失调性疾病进行综述,概括介绍与ART相关的印迹基因失调性疾病,如Beckwith-Wiedemann综合征、Prader-willi综合征、Angelman综合征、Silver-Russell综合征等的发病率及相关机制。     

卵子发育过程中组蛋白的动态变化

表观遗传修饰是指不改变DNA序列的可逆性修饰,包括DNA甲基化、RNA干涉、基因组印迹和组蛋白密码等多方面,在生物体生长发育过程中对基因表达和调控有重要作用。在卵子发育过程中,卵母细胞经历了一系列的表观遗传动态修饰,这一表观遗传成熟过程对于卵子的减数分裂及发育能力至关重要。其中组蛋白的转录后修饰及不同组蛋白的替换对异染色质的形成及卵母细胞基因组重塑过程起关键作用。现对卵子发育过程中组蛋白甲基化、乙酰化、磷酸化等共价修饰及不同组蛋白替换的研究现状做一总结。     

卵子发育过程中组蛋白的动态变化

表观遗传修饰是指不改变DNA序列的可逆性修饰,包括DNA甲基化、RNA干涉、基因组印迹和组蛋白密码等多方面,在生物体生长发育过程中对基因表达和调控有重要作用.在卵子发育过程中,卵母细胞经历了一系列的表观遗传动态修饰.这一表观遗传成熟过程对于卵子的减数分裂及发育能力至关重要.其中组蛋白的转录后修饰及不同组蛋白的替换对异染色质的形成及卵母细胞基凼组重塑过程起关键作用.现对卵子发育过程中组蛋白甲基化、乙酰化、磷酸化等共价修饰及不同组蛋白替换的研究现状做一总结.     

常见组蛋白修饰调控滋养层细胞谱系分化的研究进展

胎盘是决定妊娠建立及维持胎儿正常生长发育的重要器官, 其介导了母胎间的复杂对话。滋养层细胞是执行胎盘功能的一类重要细胞类型, 在胎盘发育过程中, 滋养层干细胞可分化为多种滋养层细胞亚型, 从而维持胎盘的结构和功能。组蛋白修饰可通过调控染色质的结构及基因转录参与滋养层细胞谱系的建立和维持。本文系统性总结了重要组蛋白甲基化及乙酰化修饰调控滋养层干细胞分化及胎盘发育的复杂作用及机制。     

DNA甲基化在复发性流产病因中的研究进展

复发性流产（recurrent spontaneous abortion,RSA）是一种常见病理性妊娠,其中有约50%的患者病因和发病机制不明确。随着表观遗传学研究领域的发展,尤其是近年来DNA甲基化的研究,为RSA的病理生理机制提供了一个新视角。研究发现,基因DNA甲基化的功能缺陷、DNA的甲基化修饰调控及DNA甲基化介导的其他表观遗传修饰方式与RSA密切相关,印迹基因DNA甲基化、胎盘特有基因DNA甲基化以及精子DNA甲基化异常都直接或间接地影响胚胎的着床、生长及发育过程,最终导致RSA的发生。现阐述DNA甲基化在RSA发生、发展中的作用及其研究进展。     

脂肪酸合成酶表观遗传学调控的研究进展

脂肪酸合成酶(fatty acid synthase, FASN)在肿瘤和能量代谢性相关疾病中表达异常上升,且与多种表观遗传学调控机制相关。研究FASN的表观遗传学调控可以深入阐明FASN在疾病发生发展中的作用,为纠正异常表达的FASN提供新思路。本文综述了Fasn基因DNA甲基化、FASN mRNA甲基化和甲基化读码器蛋白、微小RNA与长链非编码RNA、组蛋白H3与H4磷酸化与乙酰化修饰以及FASN蛋白的翻译后修饰等FASN表观遗传学的调控机制,为通过表观遗传学靶点发挥对FASN的抑制作用提供新证据。     

宫内高雄激素环境与子代多囊卵巢综合征

近年研究认为,多囊卵巢综合征(polycystic ovary syndrome,PCOS)是一种胎源性疾病.胎儿暴露于宫内高雄激素环境,可能引起多个组织内基因表观遗传修饰状态的改变,如基因DNA甲基化、子代基因印迹的改变,干扰胎儿下丘脑-垂体-卵巢轴和内脏靶器官的生理发育过程,导致下丘脑对类固醇激素的负反馈调节敏感性下降和胰腺功能受损,造成青春期或成年后出现各种PCOS症状.明确PCOS的早期发病机制,对预防高危人群PCOS的发生与发展具有临床意义.     

神经胶质瘤的表观遗传学机制

神经胶质瘤是颅内最常见的一种恶性肿瘤,它的发生、发展与表观遗传修饰密切相关。本文着重介绍了近年来神经胶质瘤发生、发展过程中DNA甲基化异常、miRNA表达异常、组蛋白修饰异常三种主要的表观遗传修饰方式的研究进展。由于表观遗传修饰引起的改变可以通过药物逆转,本文进而探讨了基于表观遗传修饰机制的潜在药物治疗神经胶质瘤的前景。     

镉表观遗传毒性研究进展

镉是一种常见的重金属毒物,工业上含镉化合物产品的广泛使用不可避免地会导致镉的环境污染,并主要通过食物链进入机体。镉对生物体的毒作用包括肝肾损伤、神经内分泌、生殖发育及致癌致畸等方面,并且可能与发育源性疾病间具有紧密的关联。表观遗传可以在不改变DNA序列的情况下调控基因的表达,主要方式包括DNA甲基化、组蛋白修饰、非编码RNA调控(ncRNA)。遗传学机制已被证实是含镉化学物发挥毒作用的重要机制,但近年来的研究表明表观遗传学修饰在调控镉的毒效应中的作用可能更为重要。因此,本文对表观遗传修饰的变化在镉发挥毒性效应中的作用作一综述。     

Prospects for Epigenetic Epidemiology

Epigenetic modification can mediate environmental influenceson gene expression and can modulate the disease risk associatedwith genetic variation. Epigenetic analysis therefore holdssubstantial promise for identifying mechanisms through whichgenetic and environmental factors jointly contribute to diseaserisk. The spatial and temporal variance in epigenetic profileis of particular relevance for developmental epidemiology andthe study of aging, including the variable age at onset formany common diseases. This review serves as a general introductionto the topic by describing epigenetic mechanisms, with a focuson DNA methylation; genetic and environmental factors that influenceDNA methylation; epigenetic influences on development, aging,and disease; and current methodology for measuring epigeneticprofile. Methodological considerations for epidemiologic studiesthat seek to include epigenetic analysis are also discussed. DNA methylation; environment; epigenesis, genetic; folic acid     

Epigenetic regulation during mammalian oogenesis

The advent of the epigenetic era has sparked a new frontier in molecular research and the understanding of how development can be regulated beyond direct alterations of the genome. Thus far, the focal point of epigenetic regulation during development has been chromatin modifications that control differential gene expression by DNA methylation and histone alterations. But what of events that alter gene expression without direct influence on the DNA itself? The present review focuses on epigenetic pathways regulating development from oogenesis to organogenesis and back that do not involve methylation of cytosine in DNA. We discuss target components of epigenetic modification such as organelle development, compartmentalisation of maternal factors and molecular mediators in the oocyte and how these factors acting during oogenesis impact on later development. Epigenetic regulation of development, be it via cytosine methylation or not, has wide-ranging effects on the subsequent success of a pregnancy and the intrinsic health of offspring. Perturbations in epigenetic regulation have been clearly associated with disease states in adult offspring, including Type II diabetes, hypertension, cancers and infertility. A clear understanding of all epigenetic mechanisms is paramount when considering the increased use of assisted reproductive techniques and the risks associated with their use.     

Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease

The burgeoning interest in the field of epigenetics has precipitated the need to develop approaches to strengthen causal inference when considering the role of epigenetic mediators of environmental exposures on disease risk. Epigenetic markers, like any other molecular biomarker, are vulnerable to confounding and reverse causation. Here, we present a strategy, based on the well-established framework of Mendelian randomization, to interrogate the causal relationships between exposure, DNA methylation and outcome. The two-step approach first uses a genetic proxy for the exposure of interest to assess the causal relationship between exposure and methylation. A second step then utilizes a genetic proxy for DNA methylation to interrogate the causal relationship between DNA methylation and outcome. The rationale, origins, methodology, advantages and limitations of this novel strategy are presented.     

Nutritional Epigenomics: A Portal to Disease Prevention

Epigenetics can be defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence. Epigenomics is the study of genome-wide epigenetic modifications. Because gene expression changes are critical in both normal development and disease progression, epigenetics is widely applicable to many aspects of biological research. The influences of nutrients and bioactive food components on epigenetic phenomena such as DNA methylation and various types of histone modifications have been extensively investigated. Because an individual’s epigenetic patterns are established during early gestation and are changed and personalized by environmental factors during our lifetime, epigenetic mechanisms are quite important in the development of transgenerational and adult obesity as well as in the development of diabetes mellitus. Aging and cancer demonstrate profound genome-wide DNA methylation changes, suggesting that nutrition may affect the aging process and cancer development through epigenetic mechanisms.     

Nutrition and epigenetics: An emerging field

Epigenetics refers to heritable changes to gene expression encoded not by differences in the genetic sequence but by other chemical modifications to chromatin, such as methylation of the DNA backbone, or acetylation and methylation of the histone core. The total set of such epigenetic marks can be referred to as the epigenome, but unlike the genome, epigenetic marks differ between tissues and are modified by metabolic conditions and environmental exposures throughout life. In humans and animal models, key metabolic pathways, such as those of energy metabolism and obesity, are believed to be partly regulated by epigenetic mechanisms and to be subject to metabolic and nutritional modification in utero and throughout life. There is growing interest in the possibility that extremes of energy or micronutrient availability may modulate the epigenome and hence modify the development and disease susceptibility of individuals. Particular interest is evident for methyl donors, including folic acid, which might directly modify DNA methylation in humans.     

表观遗传异常与宫颈癌

摘要:癌症是一类遗传及表观遗传异常的复杂疾病。宫颈癌由癌前病变发展为侵入性的宫颈癌是由于人乳头瘤病毒（Human Papilloma Virus,HPV）持续感染引起了宿主基因组及表观遗传基因组的改变。表观遗传改变包括DNA甲基化水平改变、miRNA异常表达、癌基因的激活及抑癌基因沉默等。鉴于miRNA可被表观遗传机制调控,因而其在宫颈癌中的异常表达可能是启动子甲基化水平改变引起的。基于以上判断,本文对HPV感染、DNA甲基化水平改变及miRNA异常表达间的关系进行综述,以期揭示表观遗传异常与宫颈癌发生发展之间的关系。     

环境表观遗传学研究进展

在许多复杂疾病如肿瘤、心血管系统疾病等的发生发展过程中,遗传学机制和环境因素均发挥着重要的作用。遗传学的核心研究内容集中在基因突变、基因重组等基因序列的改变,而目前的研究发现除基因序列外,还存在着其他一些因素影响着基因的表达。表观遗传学即是研究除基因序列改变之外,基因功能的可逆的、可遗传的改变,主要有DNA甲基化、组蛋白乙酰化、微小RNA等。随着环境医学研究的不断深入,表观遗传的重要作用得以凸显,表观遗传的改变不仅可以解释某些疾病的发病机制,而且还可以作为疾病早期诊断和预防的标志。环境中化学因素、物理因素、生物因素和精神心理以及其他因素的表观遗传学改变已被证实与疾病密切相关,因此了解环境中各种因素的表观遗传效应十分必要。     

子宫内膜异位症不孕的表观遗传学研究进展

子宫内膜异位症是生育年龄妇女不孕的主要原因之一,其机制仍不清楚.最新研究发现,子宫内膜异位症可能是一种表观遗传性疾病.DNA甲基化异常和印记功能紊乱是表现遗传异常的主要形式.在子宫内膜异位症中存在DNA的异常甲基化,这种异常甲基化与子宫内膜异位症不孕有关;印记基因对胎儿及胎盘的发育具有十分重要的作用,子宫内膜异位症相关的印记功能紊乱可能影响胚胎着床和发育.该文就DNA甲基化、基因印记与子宫内膜异位症不孕的研究进展作以综述,为子宫内膜异位症不孕新治疗方法的提出提供理论依据.     

Nutritional Status Impacts Epigenetic Regulation in Early Embryo Development: A Scoping Review

With the increasing maternal age and the use of assisted reproductive technology in various countries worldwide, the influence of epigenetic modification on embryonic development is increasingly notable and prominent. Epigenetic modification disorders caused by various nutritional imbalance would cause embryonic development abnormalities and even have an indelible impact on health in adulthood. In this scoping review, we summarize the main epigenetic modifications in mammals and the synergies among different epigenetic modifications, especially DNA methylation, histone acetylation, and histone methylation. We performed an in-depth analysis of the regulation of various epigenetic modifications on mammals from zygote formation to cleavage stage and blastocyst stage, and reviewed the modifications of key sites and their potential molecular mechanisms. In addition, we discuss the effects of nutrition (protein, lipids, and one-carbon metabolism) on epigenetic modification in embryos and emphasize the importance of various nutrients in embryonic development and epigenetics during pregnancy. Failures in epigenetic regulation have been implicated in mammalian and human early embryo loss and disease. With the use of reproductive technologies, it is becoming even more important to establish developmentally competent embryos. Therefore, it is essential to evaluate the extent to which embryos are sensitive to these epigenetic modifications and nutrition status. Understanding the epigenetic regulation of early embryo development will help us make better use of reproductive technologies and nutrition regulation to improve reproductive health in mammals.