2012年10月15日 訊 /生物谷BIOON/ --理解我們DNA上的化學(xué)標(biāo)記如何影響基因表達(dá)可能是科學(xué)家們而言是非常重要的。DNA上常見(jiàn)的一種化學(xué)標(biāo)記就是甲基化,。
在一項(xiàng)新研究中,，來(lái)自加拿大西蒙弗雷澤大學(xué)、英屬哥倫比亞大學(xué)和美國(guó)斯坦福大學(xué)的研究人員發(fā)現(xiàn)在一個(gè)人群中,，甲基化變異性能夠預(yù)測(cè)年齡,、性別、壓力,、癌癥和早年的社會(huì)經(jīng)濟(jì)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(kāi)啟或關(guān)閉,?；虮磉_(dá)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(xiàng)研究中,，Eldon Emberly和同事們研究了一個(gè)大的群體中的甲基化變異性,。他們測(cè)量了來(lái)自92個(gè)人(年齡在24到45歲)的白細(xì)胞中的DNA甲基化。Emberly實(shí)驗(yàn)室對(duì)產(chǎn)生的數(shù)據(jù)集進(jìn)行分析來(lái)尋找甲基化變異與實(shí)驗(yàn)參與者的不同社會(huì),、精神和身體特征之間存在的關(guān)聯(lián)性,。
研究結(jié)果證實(shí)童年時(shí)代經(jīng)歷貧窮的那些人擁有的甲基化水平與沒(méi)有類(lèi)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(huì)經(jīng)濟(jì)地位,。這就意味著早年的生活環(huán)境在一個(gè)人的DNA中留下可檢測(cè)的分子標(biāo)記,。
DNA甲基化與基因表達(dá)之間存在的關(guān)聯(lián)是非常復(fù)雜的，這是因?yàn)樗⒉豢偸强深A(yù)測(cè)的,，但是總是存在一種特定的關(guān)聯(lián),。
Emberly說(shuō)，“甲基化變異性與基因DDX4表達(dá)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(shuō)，這項(xiàng)研究發(fā)現(xiàn)也提出一些有意思的問(wèn)題,，這是因?yàn)榧谆鸵恍┲T如吸煙和飲酒之類(lèi)的特征之間的關(guān)聯(lián)要比預(yù)測(cè)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(lèi)型中的甲基化是否更好地預(yù)測(cè)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.
