2012年10月15日 訊 /生物谷BIOON/ --理解我們DNA上的化學標記如何影響基因表達可能是科學家們而言是非常重要的,。DNA上常見的一種化學標記就是甲基化,。
在一項新研究中，來自加拿大西蒙弗雷澤大學,、英屬哥倫比亞大學和美國斯坦福大學的研究人員發(fā)現(xiàn)在一個人群中,，甲基化變異性能夠預(yù)測年齡、性別,、壓力,、癌癥和早年的社會經(jīng)濟地位。相關(guān)研究結(jié)果于近期刊登在PNAS期刊上,。
已知在我們的基因組中,，發(fā)生甲基化的DNA影響基因是否開啟或關(guān)閉?；虮磉_能夠推斷與我們的身份相關(guān)聯(lián)的幾種屬性,，如性別,、種族、年齡和健康,。
在這項研究中，Eldon Emberly和同事們研究了一個大的群體中的甲基化變異性,。他們測量了來自92個人(年齡在24到45歲)的白細胞中的DNA甲基化,。Emberly實驗室對產(chǎn)生的數(shù)據(jù)集進行分析來尋找甲基化變異與實驗參與者的不同社會、精神和身體特征之間存在的關(guān)聯(lián)性,。
研究結(jié)果證實童年時代經(jīng)歷貧窮的那些人擁有的甲基化水平與沒有類似經(jīng)歷的那些人中的不同,。盡管參與研究的這些人在以后的生活中都獲得了相同的社會經(jīng)濟地位。這就意味著早年的生活環(huán)境在一個人的DNA中留下可檢測的分子標記,。
DNA甲基化與基因表達之間存在的關(guān)聯(lián)是非常復(fù)雜的,，這是因為它并不總是可預(yù)測的，但是總是存在一種特定的關(guān)聯(lián),。
Emberly說,，“甲基化變異性與基因DDX4表達的變異性相關(guān)聯(lián)，而基因DDX4與某些癌癥相關(guān)聯(lián),。”
Emberly說,，這項研究發(fā)現(xiàn)也提出一些有意思的問題，這是因為甲基化和一些諸如吸煙和飲酒之類的特征之間的關(guān)聯(lián)要比預(yù)測中的要弱,，或者是不存在的,。
如今，研究人員正在在不同組織類型中的甲基化是否更好地預(yù)測一些特征,。(生物谷Bioon.com)
doi: 10.1073/pnas.1121249109
PMC:
PMID:
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.
