自從人類基因組測序的完成，有一個問題已經(jīng)長時間阻礙了基因調(diào)控（gene control）的科學(xué)研究，即人類是如何復(fù)雜于酵母這類低等生物的,，這是否與我們基因組中的一些基因調(diào)控蛋白有關(guān)呢？
約翰霍普金斯醫(yī)學(xué)院的研究人員通過檢測整個基因組中蛋白-DNA互作,，發(fā)現(xiàn)有300多個蛋白能夠調(diào)控基因,，這項新發(fā)現(xiàn)說明，先前所有已知的蛋白在細胞中還承擔著其他的角色,。這項研究結(jié)果發(fā)布在10月30日的Cell上,，為人類復(fù)雜于酵母提供了部分解釋。
Heng Zhu博士介紹說,，轉(zhuǎn)錄因子能夠以序列特異性的方式綁定到DNA上,。但是這只是我們表面上能夠觀察到的，其實我們發(fā)現(xiàn)還有一些蛋白能夠潛在作為二線轉(zhuǎn)錄因子,。
研究小組猜測,，可能有更多基因組編碼的蛋白同樣能夠在二線調(diào)控基因，所以研究人員認為,，相對簡單的生物,，比如植物，它們似乎比人類有更多的轉(zhuǎn)錄因子,。
此外,，可能我們的大部分基因進行著雙重，三重或四重的運作,，Zhu介紹說,，這可能是人類中存在的一個普遍現(xiàn)象，或許也是人類復(fù)雜于其他生物而并沒有明顯多的基因的原因,。
研究小組開始著手確定哪些基因組編碼的蛋白能綁定到哪些特定的DNA序列上,。他們檢測了人類基因子上1,400到1,700個能夠綁定到DNA上并能打開或關(guān)閉基因的轉(zhuǎn)錄因子,，此外還包括一些其他類型的蛋白，如維持染色體結(jié)構(gòu)并能綁定到結(jié)構(gòu)特異的RNA上的蛋白,，在細胞內(nèi)傳遞信息但不會直接和DNA接觸的蛋白,。在蛋白質(zhì)芯片上，總共收集了將近4,200種人類的蛋白,。
為了識別芯片上能夠直接綁定DNA的蛋白,，研究小組查閱了之前的科學(xué)文獻，并記錄了460段不同的短序列DNA,，這些序列是已知的或被預(yù)測能夠連接蛋白的,。研究人員將每一段DNA序列與蛋白質(zhì)芯片進行測試。除了發(fā)現(xiàn)許多轉(zhuǎn)錄因子的蛋白質(zhì)-DNA互作和一些先前證實的互作外,，還發(fā)現(xiàn)了367種新的非傳統(tǒng)DNA綁定蛋白,。
研究人員介紹說，這項發(fā)現(xiàn)幾乎將蛋白-DNA互作的數(shù)量增加了1倍,，但是他們只是考察了所有人類蛋白中的1/5,，可能還有數(shù)百甚至數(shù)千的更多像這類非傳統(tǒng)的轉(zhuǎn)錄因子存在，而這還是未知的,。其中一個非傳統(tǒng)的轉(zhuǎn)錄因子是MAP激酶1,，也就是ERK2。這是一種已經(jīng)被深入研究過的蛋白,，能夠控制細胞生長和發(fā)育,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell,30 October 2009 doi:10.1016/j.cell.2009.08.037
Profiling the Human Protein-DNA Interactome Reveals ERK2 as a Transcriptional Repressor of Interferon Signaling
Shaohui Hu1, 4, 9, Zhi Xie2, 9, Akishi Onishi3, 4, 5, Xueping Yu2, Lizhi Jiang3, 4, 5, Jimmy Lin6, Hee-sool Rho1, 4, Crystal Woodard1, 4, Hong Wang3, 4, 5, Jun-Seop Jeong1, 4, Shunyou Long4, Xiaofei He1, 4, Herschel Wade7, Seth Blackshaw2, 3, 4, 5, , , Jiang Qian2, 8, , and Heng Zhu1, 4, 8, ,
1 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
4 The Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5 Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
6 Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
7 Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
8 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Protein-DNA interactions (PDIs) mediate a broad range of functions essential for cellular differentiation, function, and survival. However, it is still a daunting task to comprehensively identify and profile sequence-specific PDIs in complex genomes. Here, we have used a combined bioinformatics and protein microarray-based strategy to systematically characterize the human protein-DNA interactome. We identified 17,718 PDIs between 460 DNA motifs predicted to regulate transcription and 4,191 human proteins of various functional classes. Among them, we recovered many known PDIs for transcription factors (TFs). We identified a large number of unanticipated PDIs for known TFs, as well as for previously uncharacterized TFs. We also found that over three hundred unconventional DNA-binding proteins (uDBPs)–which include RNA-binding proteins, mitochondrial proteins, and protein kinases–showed sequence-specific PDIs. One such uDBP, ERK2, acts as a transcriptional repressor for interferon gamma-induced genes, suggesting important biological roles for such proteins.
