组蛋白甲基化修饰在子宫内膜癌中的研究进展

子宫内膜癌是一种子宫内膜上皮源性的恶性肿瘤。雌激素刺激、肥胖、糖尿病、高血压和未孕未产等因素是其发病的高危因素。近年研究发现,表观遗传修饰在子宫内膜癌中起重要作用。随着组蛋白甲基化修饰在子宫内膜癌中的研究逐渐深入,越来越多的研究发现组蛋白甲基化修饰作为基因转录的重要一环具有复杂的生物学行为。组蛋白甲基化相关的酶与癌症的发生密切相关,其可能通过调节启动子、增强子、外显子和重复序列等基因结构的组蛋白甲基化,使下游基因重编程,从而在子宫内膜癌的发生、发展及预后中发挥重要作用。未来有望通过靶向组蛋白甲基化相关的酶来调节基因的生物学行为,从而预防和治疗子宫内膜癌。     

宫颈癌中表观遗传学的研究进展

表观遗传学(epigenetics)是分子生物学的一个重要分支,重点研究基因甲基化,组蛋白修饰等引起的基因表达的改变。近来研究显示,人乳头状瘤病毒(HPV)和细胞内基因组在宫颈癌各阶段都发生了改变,包括:整个基因的低甲基化,关键抑癌基因的高甲基化及组蛋白修饰,其表观改变发生在致癌过程的早期阶段。该研究进展有助于宫颈癌的早期诊断,也为分子靶向治疗宫颈癌提供了可能。     

宫颈癌中表观遗传学的研究进展

表观遗传学(epigenetics)是分子生物学的一个重要分支,重点研究基因甲基化,组蛋白修饰等引起的基因表达的改变.近来研究显示,人乳头状瘤病毒(HPV)和细胞内基因组在宫颈癌各阶段都发生了改变,包括:整个基因的低甲基化,关键抑癌基因的高甲基化及组蛋白修饰,其表观改变发生在致癌过程的早期阶段.该研究进展有助于宫颈癌的早期诊断,也为分子靶向治疗宫颈癌提供了可能.     

子宫内膜容受性的表观遗传调控机制的研究进展

表观遗传在调控子宫内膜容受性和胚胎植入方面有重要作用。表观遗传学调控参与月经周期子宫内膜再生和增殖、血管形成、植入和蜕膜化。DNA甲基化与EMs发生有关,卵巢癌相关的肿瘤抑制基因的高甲基化导致基因表达沉默,很多与子宫内膜癌相关的肿瘤基因都有异常甲基化变化,进而发生肿瘤。组蛋白修饰参与许多妇科疾病的发生过程,其中部分妇科疾病正是因为改变子宫内膜容受状态进而导致不孕。组蛋白修饰和DNA甲基化之间也可以相互调控,同时组蛋白乙酰化也可以调节DNA甲基化。缺少miRNA的表达与某些人类子宫内膜疾病相关,例如EMs、子宫内膜增生和肿瘤,这些疾病影响子宫内膜的厚度、血流状态、分子表达进而降低子宫内膜的容受性,导致不孕。     

组蛋白修饰酶与子宫内膜癌发生发展关系的研究进展

表观遗传学是研究没有细胞核DNA序列改变的情况时基因功能可逆的、可遗传的改变。这些改变包括DNA甲基化、组蛋白修饰、微小RNA（micro RNA）和基因组印迹等。组蛋白是核小体的关键成分,组蛋白修饰在遗传学中意义重大。组蛋白修饰酶与人类肿瘤的关系日渐成为研究热点,而在子宫内膜癌领域相关研究较少。现对近5年来相关文献进行汇总,从组蛋白乙酰化、组蛋白甲基化、组蛋白修饰与DNA甲基化关系三个方面着手,阐述组蛋白修饰酶与子宫内膜癌的研究进展。     

表观遗传学与宫颈癌的研究进展

随着对肿瘤发病机制的逐步深入研究,人们认识到表观遗传学这些DNA序列以外的调控机制异常在肿瘤的发生、发展过程中起了重要作用。DNA甲基化、micro RNA表达调控及组蛋白的修饰等表观遗传机制是宫颈癌发生、发展的重要原因之一。表观遗传学的研究进展不仅有助于宫颈癌的早期诊断,对于分子靶向治疗宫颈癌亦具有良好的应用前景。     

DNA甲基化和组蛋白修饰对反复自然流产的影响

近年来,越来越多的研究表明表观遗传学(epigenetics)与多种疾病密切相关。而胚胎发育的不健全是导致自然流产的重要原因。本文中,我们通过探讨表观遗传学中DNA甲基化和组蛋白修饰与胚胎发育的关系,阐明表观遗传学对反复自然流产(recurrent spontaneous abortion,RSA)的影响,并概述最近几年在动物和人类研究中的进展。     

基因甲基化在卵巢癌中的研究进展

基因甲基化是基因正常的修饰形式,但是异常基因甲基化是基因失活的一种重要机制,对肿瘤的发生及其发展有重要影响,表现为在肿瘤细胞中整体甲基化程度降低和局部甲基化程度的增高。研究发现许多抑癌基因启动子区域CpG超甲基化与卵巢癌的关系密切。主要就抑癌基因超甲基化与卵巢癌在早期发现、诊断、治疗和预测癌细胞的转移、复发以及提高对抗癌药的敏感性等方面的研究现状作一探讨,并对基因甲基化的研究方向作简要描述。     

支气管肺发育不良的表观遗传学机制研究进展

支气管肺发育不良是早产儿常见的慢性呼吸系统并发症,其发病机制尚未完全阐明,且暂无有效防治措施,严重影响早产儿存活率及预后。已有研究证实,组蛋白修饰、非编码RNA和DNA甲基化等表观遗传学机制在支气管肺发育不良的发生、发展过程中发挥重要作用,且相关表观遗传变化多为可逆性改变,可能为临床治疗提供重要靶点。因此,表观遗传学研究将为进一步认识支气管肺发育不良的发病机制及防治支气管肺发育不良提供新方向和思路。     

基因甲基化在卵巢癌中的研究进展

基因甲基化是基因正常的修饰形式,但是异常基因甲基化是基因失活的一种重要机制,对肿瘤的发生及其发展有重要影响,表现为在肿瘤细胞中整体甲基化程度降低和局部甲基化程度的增高.研究发现许多抑癌基因启动子区域CpG超甲基化与卵巢癌的关系密切.主要就抑癌基因超甲基化与卵巢癌在早期发现、诊断、治疗和预测癌细胞的转移、复发以及提高对抗癌药的敏感性等方面的研究现状作一探讨,并对基因甲基化的研究方向作简要描述.     

Epigenetics of sex determination in mammals

Epigenetics is the study of changes in gene function that cannot be explained by changes in DNA sequence. A mammalian body contains more than two hundred types of cells. Since all of them are derived from a single fertilized egg, their genotypes are identical. However, the gene expression patterns are different between the cell types, indicating that each cell type has unique own “epigenotype”. Epigenetic gene regulation mechanisms essentially contribute to various processes of mammalian development. The essence of epigenetic regulation is the structural change of chromatin to modulate gene activity in a spatiotemporal manner. DNA methylation and histone modifications are the major epigenetic mechanisms. Sex determination is the process for gender establishment. There are two types of sex-determining mechanisms in animals, environmental sex determination (ESD) and genotypic sex determination (GSD). Recent studies have provided some evidence that epigenetic mechanisms play indispensable roles in ESD and GSD. Some fishes undergo ESD, in which DNA methylation is essentially involved. GSD is employed in therian mammals, where Sry (sex-determining region on the Y chromosome) triggers testis differentiation from undifferentiated gonads. Sry expression is tightly regulated in a spatiotemporal manner. A recent study demonstrated that histone modification is involved in Sry regulation. In this review, we discuss the role of epigenetic mechanisms for sex determination in mammals and other vertebrates.     

The epigenetics of ovarian cancer drug resistance and resensitization

Ovarian cancer is the most lethal of all gynecologic neoplasms. Early-stage malignancy is frequently asymptomatic and difficult to detect and thus, by the time of diagnosis, most women have advanced disease. Most of these patients, although initially responsive, eventually develop and succumb to drug-resistant metastases. The success of typical postsurgical regimens, usually a platinum/taxane combination, is limited by primary tumors being intrinsically refractory to treatment and initially responsive tumors becoming refractory to treatment, due to the emergence of drug-resistant tumor cells. This review highlights a prominent role for epigenetics, particularly aberrant DNA methylation and histone acetylation, in both intrinsic and acquired drug-resistance genetic pathways in ovarian cancer. Administration of therapies that reverse epigenetic "silencing" of tumor suppressors and other genes involved in drug response cascades could prove useful in the management of drug-resistant ovarian cancer patients. In this review, we summarize recent advances in the use of methyltransferase and histone deacetylase inhibitors and possible synergistic combinations of these to achieve maximal tumor suppressor gene re-expression. Moreover, when used in combination with conventional chemotherapeutic agents, epigenetic-based therapies may provide a means to resensitize ovarian tumors to the proven cytotoxic activities of conventional chemotherapeutics.     

去乙酰化酶抑制剂抗肿瘤作用研究进展

表观遗传修饰在肿瘤中起重要作用,对基因表达有重要影响的是染色质组蛋白乙酰化,依靠组蛋白乙酰化转移酶（histone acetyltransferases,HATs）和组蛋白去乙酰化酶（histone deacetylases,HDACs）的调控来平衡。染色质的乙酰化状态能导致肿瘤抑制基因或促凋亡基因低表达。组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitors,HDACi）可通过提高染色质特定区域组蛋白乙酰化,从而影响基因的表达,成为一类新的抗肿瘤药物。HDACi具有诱导细胞周期抑制和凋亡的抗肿瘤潜能。已有几种HDACi进入临床试验阶段。     

Roles of epigenome in mammalian spermatogenesis

Mammalian spermatogenesis is a successive process consisting of spermatogonial proliferation, spermatocytic meiosis, and spermiogenesis, representing the maturation of haploid spermatids. During the process, 25–75 % of the expected sperm yield is thought to be lost through apoptosis. In addition, spermatogenesis is considered to be a process undergoing successive heterochromatinization, finally reaching a complete condensed form in the sperm head. Thus, cell proliferation, differentiation and death may be strictly regulated by epigenetic factors in this process. This review describes the current understanding of the role of epigenome in spermatogenesis, especially focusing on the following aspects; DNA methylation, modification of histones, and small RNA function. These epigenetic factors affect each other and play a central role in events essential for spermatogenesis, fertilization and embryogenesis, through the regulation of gene expression, transposon activities, meiotic sex chromosome inactivation, histone remodeling and genome imprinting. Finally, a brief discussion of future avenues of study is highlighted.     

Heterogeneous distribution of histone methylation in mature human sperm

Purpose

To analyze the presence of various histone modifications in ejaculated human spermatozoa

Methods

In this prospective study, seminal ejaculates from 39 normozoospermic individuals were evaluated for semen analysis and the presence of histone modifications in isolated nuclei.

Results

We observed heterogeneous presence of histone methylation in normal mature human sperm. We observed that 12 to 30 % of the nuclei of normal sperm contain a heterogeneous distribution of the marks H3K4Me1, H3K9Me2, H3K4Me3, H3K79Me2, and H3K36Me3. Moreover, the presence of these marks is higher in the poor motile fraction of the ejaculate, which is associated with poor morphology and functional quality. In contrast, we did not observe histone acetylation (H3K4Ac and H4K5Ac) in normal or abnormal mature human sperm

Conclusions

Defects in the process of spermatogenesis may alter the correct epigenetic programing in mature sperm. Further studies are required to evaluate the impact of these findings in human infertility