2012年10月15日 讯 /生物谷BIOON/ --理解我们DNA上的化学标记如何影响基因表达可能是科学家们而言是非常重要的。DNA上常见的一种化学标记就是甲基化。
在一项新研究中，来自加拿大西蒙弗雷泽大学、英属哥伦比亚大学和美国斯坦福大学的研究人员发现在一个人群中，甲基化变异性能够预测年龄、性别、压力、癌症和早年的社会经济地位。相关研究结果于近期刊登在PNAS期刊上。
已知在我们的基因组中，发生甲基化的DNA影响基因是否开启或关闭。基因表达能够推断与我们的身份相关联的几种属性，如性别、种族、年龄和健康。
在这项研究中，Eldon Emberly和同事们研究了一个大的群体中的甲基化变异性。他们测量了来自92个人(年龄在24到45岁)的白细胞中的DNA甲基化。Emberly实验室对产生的数据集进行分析来寻找甲基化变异与实验参与者的不同社会、精神和身体特征之间存在的关联性。
研究结果证实童年时代经历贫穷的那些人拥有的甲基化水平与没有类似经历的那些人中的不同。尽管参与研究的这些人在以后的生活中都获得了相同的社会经济地位。这就意味着早年的生活环境在一个人的DNA中留下可检测的分子标记。
DNA甲基化与基因表达之间存在的关联是非常复杂的，这是因为它并不总是可预测的，但是总是存在一种特定的关联。
Emberly说，“甲基化变异性与基因DDX4表达的变异性相关联，而基因DDX4与某些癌症相关联。”
Emberly说，这项研究发现也提出一些有意思的问题，这是因为甲基化和一些诸如吸烟和饮酒之类的特征之间的关联要比预测中的要弱，或者是不存在的。
如今，研究人员正在在不同组织类型中的甲基化是否更好地预测一些特征。(生物谷Bioon.com)
doi: 10.1073/pnas.1121249109
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Factors underlying variable DNA methylation in a human community cohort
Lucia L. Lama, Eldon Emberlyb, Hunter B. Fraserc, Sarah M. Neumanna, Edith Chend, Gregory E. Millerd,1, and Michael S. Kobor
Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression. We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated.
