我們基因的表達(dá)可能會(huì)受到我們DNA上的特定標(biāo)記的影響,例如那些通過(guò)對(duì)特定核苷酸堿基對(duì)的甲基化而被賦予的標(biāo)記——這一過(guò)程被稱為表觀遺傳學(xué)過(guò)程,??茖W(xué)家們現(xiàn)在提出了一個(gè)詳細(xì)的圖譜用以闡釋在發(fā)育中的哺乳動(dòng)物大腦中的甲基化如何隨著時(shí)間的推移而變化。在我們很小的時(shí)候及在我們的神經(jīng)環(huán)路正在成形時(shí),,DNA甲基化會(huì)發(fā)生在我們大腦的神經(jīng)元中,;事實(shí)上,甲基化被認(rèn)為與腦發(fā)育,、學(xué)習(xí)及記憶等方面有關(guān)聯(lián),。與此同時(shí),盡管人們對(duì)發(fā)育時(shí)的表觀遺傳修飾一直有很大的興趣,,但很少有研究對(duì)其特點(diǎn)進(jìn)行描述?,F(xiàn)在,,Ryan Lister及其同事用一種新的方法分析了在小鼠及人類(lèi)腦發(fā)育中的全基因組范圍內(nèi)的DNA甲基化改變,,而不是像許多過(guò)去做過(guò)的研究那樣僅僅關(guān)注甲基化的熱點(diǎn)。通過(guò)考察在多個(gè)發(fā)育階段(胎兒,、出生后早期及成年時(shí))的神經(jīng)元,,研究人員繪制出了由DNA甲基化的特殊類(lèi)型所致的基因組范圍內(nèi)的修飾,,其中包括DNA胞嘧啶甲基化(5mC),以及衍生的甲基基團(tuán),,mCH,。他們用這一圖譜確定了腦中甲基化的幾個(gè)有趣的特征,其中一個(gè)是,,在人的頭2年生命中,mCH在其神經(jīng)元中有明顯的積累,,此后有所減緩,,但最終會(huì)在成年人中成為最常見(jiàn)的甲基基團(tuán),。在人類(lèi)神經(jīng)回路發(fā)育最快時(shí)(當(dāng)我們非常小的時(shí)候)的mCH的普遍性提示,,這一表觀遺傳影響在早期發(fā)育中是重要的,;事實(shí)上,,這種甲基化被刪除的未出生的小鼠會(huì)出現(xiàn)運(yùn)動(dòng)缺陷并死亡,。由Lister等人所做出的這一發(fā)現(xiàn)及其它發(fā)現(xiàn)提示,,甲基化標(biāo)記在大腦發(fā)育的過(guò)程中是呈動(dòng)態(tài)存在的。在此創(chuàng)建的基因組范圍內(nèi)的圖譜為人們更深入地了解大腦中的表觀遺傳修飾如何帶來(lái)完全分化的神經(jīng)系統(tǒng)鋪平了道路。這項(xiàng)研究的結(jié)果還將為今后的針對(duì)大腦中DNA甲基化的研究提供一個(gè)有用的參照工具,。(生物谷 Bioon.com)
生物谷推薦的英文摘要
Science DOI: 10.1126/science.1237905
Global Epigenomic Reconfiguration During Mammalian Brain Development
Ryan Lister, Eran A. Mukamel, Joseph R. Nery, Mark Urich, Clare A. Puddifoot, Nicholas D. Johnson, Jacinta Lucero, Yun Huang, Andrew J. Dwork, Matthew D. Schultz, Miao Yu, Julian Tonti-Filippini, Holger Heyn, Shijun Hu, Joseph C. Wu, Anjana Rao, Manel Esteller, Chuan He, Fatemeh G. Haghighi, Terrence J. Sejnowski, M. Margarita Behrens, Joseph R. Ecker
DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Finally, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain, and that CG demethylation at these hmC-poised loci depends on Tet2 activity.