人類基因組測(cè)序已產(chǎn)生大量基因信息，但是理解每個(gè)基因的功能的目標(biāo)仍未實(shí)現(xiàn),。在一項(xiàng)新研究中,，美國(guó)伊利諾伊大學(xué)研究人員報(bào)道，利用一種他們稱作“比較表觀基因組學(xué)(comparative epigenomics)”的新方法就能夠確定基因的作用,。相關(guān)論文研究結(jié)果于2012年6月8日發(fā)表在《細(xì)胞》期刊上,。
論文通訊作者、伊利諾伊大學(xué)生物工程部門和基因組生物學(xué)研究所研究員Sheng Zhong說,，“比較表觀基因組學(xué)就是進(jìn)行DNA和組蛋白修飾的種間比較,，以便對(duì)起調(diào)節(jié)作用的基因組序列進(jìn)行標(biāo)注。”
盡管一個(gè)有機(jī)體的基因組含有它所有的基因,，然而實(shí)際上確是表觀基因組決定哪些基因表達(dá),。盡管人們長(zhǎng)期以來集中關(guān)注比較基因組學(xué)---比較相近種(similar species)的基因組，并尋找是哪些共同特征決定相同性狀如何受到調(diào)節(jié)---,，然而比較表觀遺傳學(xué)則能夠?qū)φ{(diào)節(jié)的功能提供更加深入的認(rèn)識(shí),。
Zhong領(lǐng)導(dǎo)的研究人員與來自華盛頓大學(xué)的Ting Wang和來自佐治亞大學(xué)的Harris Lewin 和Franklin West合作開展研究，他們集中研究三個(gè)物種：人類,，小鼠和豬,。通過分析多能性干細(xì)胞(pluripotent stem cell)中的9個(gè)表觀基因組標(biāo)記，他們能夠?yàn)槊總€(gè)物種構(gòu)建一張表觀基因組圖譜,。
研究小組作出結(jié)論：只要采取合適的分析程序,，人們就能夠鑒定出種間表觀基因組保守標(biāo)記。他們?nèi)缓笞C實(shí)保守的表觀遺傳標(biāo)記能夠被有效地用來標(biāo)注基因組和闡明基因組的調(diào)節(jié)性功能,。
對(duì)科學(xué)而言,，最為緊迫的問題之一就是理解基因組科學(xué)，這項(xiàng)研究揭示了一個(gè)大有希望的替代方法,。Zhong補(bǔ)充道,，“比較表觀基因組學(xué)能夠讓我們找到更多的關(guān)于我們基因組功能進(jìn)化上的線索。”(生物谷：ZinFingerNase編譯)
doi: 10.1016/j.cell.2012.04.029
PMC:
PMID:
Comparative Epigenomic Annotation of Regulatory DNA
Shu Xiao, Dan Xie, Xiaoyi Cao, Pengfei Yu, Xiaoyun Xing, Chieh-Chun Chen, Meagan Musselman, Mingchao Xie, Franklin D. West, Harris A. Lewin, Ting Wang, Sheng Zhong
Despite the explosive growth of genomic data, functional annotation of regulatory sequences remains difficult. Here, we introduce “comparative epigenomics”— interspecies comparison of DNA and histone modifications—as an approach for annotation of the regulatory genome. We measured in human, mouse, and pig pluripotent stem cells the genomic distributions of cytosine methylation, H2A.Z, H3K4me1/2/3, H3K9me3, H3K27me3, H3K27ac, H3K36me3, transcribed RNAs, and P300, TAF1, OCT4, and NANOG binding. We observed that epigenomic conservation was strong in both rapidly evolving and slowly evolving DNA sequences, but not in neutrally evolving sequences. In contrast, evolutionary changes of the epigenome and the transcriptome exhibited a linear correlation. We suggest that the conserved colocalization of different epigenomic marks can be used to discover regulatory sequences. Indeed, seven pairs of epigenomic marks identified exhibited regulatory functions during differentiation of embryonic stem cells into mesendoderm cells. Thus, comparative epigenomics reveals regulatory features of the genome that cannot be discerned from sequence comparisons alone.
