Histone methylation marks play important roles in predicting the methylation status of CpG islands

The methylation status of CpG islands is highly correlated with gene expression. Current methods for computational prediction of DNA methylation only utilize DNA sequence features. In this study, besides 35 DNA sequence features, we added four histone methylation marks to predict the methylation status of CpG islands, and improved the accuracy to 89.94%. Also we applied our model to predict the methylation pattern of all the CpG islands in the human genome, and the results are consistent with the previous reports. Our results imply the important roles of histone methylation marks in affecting the methylation status of CpG islands. H3K4me enriched in the methylation-resistant CpG islands could disrupt the contacts between nucleosomes, unravel chromatin and make DNA sequences accessible. And the established open environment may be a prerequisite for or a consequence of the function implementation of zinc finger proteins that could protect CpG islands from DNA methylation.     

CpG island methylation pattern in different human tissues and its correlation with gene expression

The study on DNA methylation pattern in different human tissues attracts increasing interest nowadays, but a systematic analysis of CpG island methylation pattern between both somatic tissues and gametocyte is still lacking. In this work, we analyzed the CpG island methylation data of sperm and other 11 somatic tissues from Human Epigenome Project, and found that the CpG island methylation profiles are highly correlated between somatic tissues, while the methylation profile in sperm is quite distinct. Furthermore, we observed that in the six tissues investigated, there is no obvious correlation between the methylation level of promoter CpG islands and corresponding gene expression across different tissues.     

Role of CpG deserts in the epigenetic transgenerational inheritance of differential DNA methylation regions

Background

Previously a variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm. The transgenerational epimutations in sperm and somatic cells identified in a number of previous studies were further investigated.

Results

The epimutations from six different environmental exposures were found to be predominantly exposure specific with negligible overlap. The current report describes a major genomic feature of all the unique epimutations identified (535) as a very low (<10 CpG/100 bp) CpG density in sperm and somatic cells associated with transgenerational disease. The genomic locations of these epimutations were found to contain DMRs with small clusters of CpG within a general region of very low density CpG. The potential role of these epimutations on gene expression is suggested to be important.

Conclusions

Observations suggest a potential regulatory role for lower density CpG regions termed “CpG deserts”. The potential evolutionary origins of these regions is also discussed.     

奶牛产奶性状与乳房炎相关基因CpG含量及分布特征的比较分析

DNA甲基化是表观遗传学的重要组成部分,基因启动子区及第一外显子区的CpG甲基化通常抑制该基因的表达,而去甲基化则促进基因表达。已有的研究发现荷斯坦牛的乳房炎指标SCC(Somatic cell count)与产奶量呈较强负相关。文章分析并比较了这两类性状的相关基因的启动子区、第一外显子、下游2 000 bp序列中CpG含量及分布特征。结果表明,乳房炎相关基因的启动子、第一外显子中CpG含量显著低于产奶性状相关基因,而两类性状基因下游2 000 bp序列中CpG含量无显著性差异。另外,文中提出了两个量化基因序列中CpG特征的指标,一个是CpG平均距离,用来衡量序列中的CpG分布;另一个是条件概率p(G|C),用以量化序列中二核苷酸CpG随碱基C出现的可能性,并对两类基因的启动子和第一外显子区域的这两个指标做了统计检验。研究结果对产奶性状与乳房炎相关基因的DNA甲基化调控研究奠定了基础。     

CpG methylation recruits sequence specific transcription factors essential for tissue specific gene expression

CG methylation is an epigenetically inherited chemical modification of DNA found in plants and animals. In mammals it is essential for accurate regulation of gene expression and normal development. Mammalian genomes are depleted for the CG dinucleotide, a result of the chemical deamination of methyl-cytosine in CG resulting in TpG. Most CG dinucleotides are methylated, but ~ 15% are unmethylated. Five percent of CGs cluster into ~ 20,000 regions termed CG islands (CGI) which are generally unmethylated. About half of CGIs are associated with housekeeping genes. In contrast, the gene body, repeats and transposable elements in which CGs are generally methylated. Unraveling the epigenetic machinery operating in normal cells is important for understanding the epigenetic aberrations that are involved in human diseases including cancer. With the advent of high-throughput sequencing technologies, it is possible to identify the CG methylation status of all 30 million unique CGs in the human genome, and monitor differences in distinct cell types during differentiation and development. Here we summarize the present understanding of DNA methylation in normal cells and discuss recent observations that CG methylation can have an effect on tissue specific gene expression. We also discuss how aberrant CG methylation can lead to cancer. This article is part of a Special Issue entitled: Chromatin in time and space.     

De novo DNA methylation at the CpG island of the zebrafish no tail gene

The zebrafish no tail gene (ntl) is indispensable for the formation of the notochord and the tail structure. Here we showed that de novo DNA methylation occurred at the CpG island of ntl. The methylation started at the segmentation stage and continued after the larval stage. However, it occurred predominantly between 14 and 48 h postfertilization, which overlaps the period in which ntl expression disappears in the notochord and the tailbud. This inverse correlation, together with the methylation-associated formation of an inaccessible chromatin structure at the ntl CpG island region, suggested the involvement of the de novo methylation in ntl repression. Since no changes in methylation patterns were observed at the CpG islands of four other zebrafish genes, there must be a mechanism in zebrafish for specific methylation of the ntl CpG island.     

昆虫JHE基因结构及与甲基化相关的CpG O/E值分析

本研究选择西方蜜蜂、黑腹果蝇、致倦库蚊和家蚕四种昆虫为例,以降解保幼激素的特异性酯酶（juvenile hormone esterase,JHE）为研究对象,首先运用NCBI的Spidey在线软件将各昆虫的JHE基因与其相应的基因组序列作比对,分别确定各昆虫JHE基因的上游2000bp的具体序列和外显子及内含子区域。发现西方蜜蜂JHE基因含有7个外显子和6个内含子,而其余三种昆虫的JHE基因均含有6个外显子和5个内含子。接着,分别统计基因各区域的CpG,G,C位点的占有量,并计算出CpG O/E值（CpG位点的实际值与期望值之间的比值）,发现各区域CpG O/E平均值的大小依次为：基因上游2000bp区>内含子区>外显子区,基因上游2000bp区的CpG O/E平均值大于1.0,而第1到第4外显子的CpG O/E平均值均只有0.8左右。表明在昆虫JHE基因中,若有CpG甲基化位点发生,应主要发生在第1到第4外显子区域。     

Common methods for cytosine methylation analysis in DNA

The review considers the methods most commonly used to detect DNA methylation, their advantages, potential limitations, and selection for various purposes. A detailed protocol is described for bisulfite treatment, which is used as a preliminary step in the majority of DNA methylation assays.     

DNA methylation variation in cloned mice

Summary: Mammalian cloning has been accomplished in several mammalian species by nuclear transfer. However, the production rate of cloned animals is quite low, and many cloned offspring die or show abnormal symptoms. A possible cause of the low success rate of cloning and abnormal symptoms in many cloned animals is the incomplete reestablishment of DNA methylation after nuclear transfer. We first analyzed tissue‐specific methylation patterns in the placenta, skin, and kidney of normal B6D2F1 mice. There were seven spots/CpG islands (0.5% of the total CpG islands detected) methylated differently in the three different tissues examined. In the placenta and skin of two cloned fetuses, a total of four CpG islands were aberrantly methylated or unmethylated. Interestingly, three of these four loci corresponded to the tissue‐specific loci in the normal control fetuses. The extent of aberrant methylation of genomic DNA varied between the cloned animals. In cloned animals, aberrant methylation occurred mainly at tissue‐specific methylated loci. Individual cloned animals have different methylation aberrations. In other words, cloned animals are by no means perfect copies of the original animals as far as the methylation status of genomic DNA is concerned. genesis 30:45–50, 2001. © 2001 Wiley‐Liss, Inc.     

Stabilization of G-quadruplex structure on vascular endothelial growth factor gene promoter depends on CpG methylation site and cation type

Background

DNA methylation at the 5-position of cytosine is an epigenetic modification of CpG dinucleotides. In addition to CpG methylation, the G-quadruplex (G4) structure has been reported as a regulator of gene expression. The identification of G4 forming sequences in CpG islands suggests an involvement of CpG-methylated G4 structures in biological processes; however, few reports have addressed the effects of CpG methylation on G4 structure.