Evidence for widespread genomic methylation in the migratory locust, Locusta migratoria (Orthoptera: Acrididae)

The importance of DNA methylation in mammalian and plant systems is well established. In recent years there has been renewed interest in DNA methylation in insects. Accumulating evidence, both from mammals and insects, points towards an emerging role for DNA methylation in the regulation of phenotypic plasticity. The migratory locust (Locusta migratoria) is a model organism for the study of phenotypic plasticity. Despite this, there is little information available about the degree to which the genome is methylated in this species and genes encoding methylation machinery have not been previously identified. We therefore undertook an initial investigation to establish the presence of a functional DNA methylation system in L. migratoria. We found that the migratory locust possesses genes that putatively encode methylation machinery (DNA methyltransferases and a methyl-binding domain protein) and exhibits genomic methylation, some of which appears to be localised to repetitive regions of the genome. We have also identified a distinct group of genes within the L. migratoria genome that appear to have been historically methylated and show some possible functional differentiation. These results will facilitate more detailed research into the functional significance of DNA methylation in locusts.     

DNA methylation and epigenetic mechanisms

Genes are essential for the transmission of genetic information from generation to generation, and this mechanism of inheritance is fully understood. Genes are also essential for unfolding the genetic program for development, but the rules governing this process are obscure. Epigenetics comprises the study of the switching on and off of genes during development, the segregation of gene activities following somatic cell division, and the stable inheritance of a given spectrum of gene activities in specific cells. Some of these processes may be explained by DNA modification, particularly changes in the pattern of DNA methylation and the heritability of that pattern. There is strong evidence that DNA methylation plays an important role in the control of gene activity in cultured mammalian cells, and the properties of a CHO mutant strain affected in DNA methylation are described. Human diploid cells progressively lose cytosine methylation during serial subculture, and this may be related to their in vitro senescence. There is also evidence that DNA modifications can be inherited through the germ line. Classical genetics is based on the study of all types of change in DNA base sequence, but the rules governing the activity of genes by epigenetic mechanisms are necessarily different. Their elucidation will depend both on a theoretical framework for development and on experimental studies at the molecular, chromosomal, and cellular levels.     

DNA甲基化与脂肪组织生长发育

DNA甲基化作为一种重要的表观遗传学修饰方式,在维持正常细胞功能、遗传印记、胚胎发育以及人类肿瘤发生中起着重要作用。DNA甲基化最重要的作用是调控基因表达,它是细胞调控基因表达的重要表观遗传机制之一。近年来的研究发现,DNA甲基化在脂肪组织生长发育以及肥胖症发生过程中发挥着重要作用。DNA甲基化通过调控脂肪细胞分化转录因子、转录辅助因子以及其他脂肪代谢相关基因的表达,从而调控脂肪组织的生长发育。该文综述了脂肪组织生长发育过程中DNA甲基化的最新研究进展,探讨了脂肪组织DNA甲基化的研究趋势和未来发展方向。     

New findings showing how DNA methylation influences diseases

In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells.Major differences have been found between differentiated cells and stem cells.Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases,such as Parkinson's disease and Huntington's disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are "silenced" by the methylation of CpG sites in some of their regions.Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition,recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting,the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence.     

DNA甲基化与植物抗逆性研究进展

DNA甲基化是真核细胞基因组重要修饰方式之一.DNA甲基化通过与转录因子相互作用或通过改变染色质结构来影响基因的表达,从表观遗传水平对生物遗传信息进行调节,在生长发育过程中起着重要的作用,而且植物DNA甲基化还参与了环境胁迫下的基因表达调控过程.本文对植物DNA甲基化的产生机制、功能,以及DNA甲基化在植物应对逆境胁迫中的作用进行综述,以更好地理解植物DNA甲基化及其对环境胁迫的响应,为植物抗逆性研究及作物遗传改良提供理论参照.     

DNA甲基化及其对植物发育的调控

DNA甲基化属于一种表观遗传修饰,主要发生在CpG双核苷酸序列中的胞嘧啶上,是在DNA甲基转移酶催化下,以S-腺苷甲硫氨酸为甲基供体,将甲基转移到胞嘧啶上,生成5-甲基胞嘧啶的一种反应。DNA甲基化在植物生长过程中具有极其重要的作用。综述了植物DNA甲基化的特征、调控机制,及其对植物基因表达影响的研究进展。     

癌症DNA甲基化调控位点的识别

DNA甲基化是一种重要的表观遗传学修饰,在基因的转录调控方面具有重要的作用。异常的DNA甲基化可以导致癌症等复杂疾病发生,癌基因相关的DNA甲基化调控位点的识别对于解析癌症的发生发展机制及识别新的癌症标记具有重要意义。本研究通过整合The Cancer Genome Atlas(TCGA)的泛癌症基因组的高通量甲基化谱和基因表达谱,识别癌基因相关的DNA甲基化调控位点。对于每种癌症分批次计算Cp G位点甲基化与相关基因表达之间的相关性,并筛选调控下游基因的Cp G位点(包括强调控位点、弱调控位点和不调控位点),结果表明仅有一半的Cp G位点对下游基因具有调控作用;对癌症间共享的调控位点的分析发现不同癌症间共享的调控位点不尽相同,表明癌症特异的甲基化调控位点的存在。进一步地,对差异甲基化和差异表达基因的功能富集分析揭示了受甲基化调控的基因确实参与了癌症发生发展相关的功能。本研究的结果是对当前甲基化调控位点集的重要补充,也是识别癌症新型分子标记特征的重要资源。     

Endosperm gene imprinting and seed development

Imprinting occurs in the endosperm of flowering plants. Endosperm, produced by fertilization of the central cell in the female gametophyte, is essential for embryo and seed development. Several imprinted genes play an important role in endosperm development. The mechanism of gene imprinting involves DNA methylation and histone modification. DNA methylation is actively removed at the imprinted alleles to be activated. Histone methylation mediated by the Polycomb group complex provides another layer of epigenetic regulation at the silenced alleles. Endosperm gene imprinting can be uncoupled from seed development when fertilization of the central cell is prevented. Imprinting may be a mechanism to ensure fertilization of the central cell thereby preventing parthenogenic development of the endosperm.     

DNA methylation in animal development

Nuclear transfer experiments have demonstrated that epigenetic mechanisms operate to limit gene expression during animal development. In somatic cells, silenced genes are associated with defined chromatin states which are characterised by hypermethylation of DNA, hypoacetylation of histones and specific patterns of methylation at distinct residues of the N-terminal tails of histone H3 and H4. This review describes the role of the DNA methylation-mediated repression system (Dnmt1's, MeCPs and MBDs and associated chromatin remodelling activities) in animal development. DNA methylation is essential for normal vertebrate development but has distinct regulatory roles in non-mammalian and mammalian vertebrates. In mammals, DNA methylation has an additional role in regulating imprinting. This suggests that epigenetic regulation is plastic in its application and should be considered in a developmental context that may be species specific.