哲學(xué)家萊布尼茨曾說過,,世界上沒有兩片完全相同的葉子,,同樣的道理,世界上沒有兩個(gè)完全相同的人,,每一個(gè)人都是獨(dú)一無二的,,是什么讓你獨(dú)一無二,斯坦福大學(xué)的一位科學(xué)家在Science和Nature上的一篇文章也許給您帶來答案,。
剛剛從耶魯大學(xué)基因組科學(xué)中心過檔去斯坦福大學(xué)的Michael Snyder博士自上任便取得好成績,,近期發(fā)表2篇高水平文章,1篇Nature,,1篇Science,。Michael Snyder目前任斯坦福大學(xué)基因組中心和個(gè)性化醫(yī)療研究中心主任。
據(jù)介紹,,每個(gè)個(gè)體的“獨(dú)一無二”性的秘密并不是蘊(yùn)藏在基因中,,而是在于DNA序列周圍的一些因子。在DNA序列周圍,,存在一系列關(guān)鍵的蛋白,,名為轉(zhuǎn)錄因子,這些轉(zhuǎn)錄因子就是控制每個(gè)人獨(dú)一無二的關(guān)鍵所在。轉(zhuǎn)錄因子控制著我們的外貌,、發(fā)育情況甚至疾病,。
與先前的研究不同的是,以往的研究往往糾結(jié)于基因本身,,這個(gè)新的研究著眼于宏觀的基因組,。Michael Snyder教授表示,后基因組時(shí)代,,我們很快就可能每個(gè)人擁有自己的基因組序列,,從基因中找出人與人之間的不同卻難以實(shí)現(xiàn),我們研究發(fā)現(xiàn),,影響人與人之間差異的是與DNA序列結(jié)合的蛋白,,它們深刻地影響基因的表達(dá)。
科學(xué)家們對10個(gè)人與10只猩猩的轉(zhuǎn)錄因子進(jìn)行研究發(fā)現(xiàn),,基因組上有15,000個(gè)供NF-kB轉(zhuǎn)錄因子結(jié)合的位點(diǎn),,有19,000個(gè)供RNA PolII結(jié)合的位點(diǎn),盡管位點(diǎn)有如此多,,但每個(gè)人的位點(diǎn)結(jié)合頻率卻不一樣,。25%的Pol II結(jié)合位點(diǎn)和7.5%的NF-kB的結(jié)合位點(diǎn)引人而異。
這些結(jié)果表明,,轉(zhuǎn)錄因子結(jié)合位點(diǎn)的差異給人類的個(gè)體帶來很大的差異,。這是每個(gè)人獨(dú)一無二的根源所在。(生物谷Bioon.com)
生物谷推薦原文出處:
Science DOI: 10.1126/science.1183621
Variation in Transcription Factor Binding Among Humans
Maya Kasowski,1,* Fabian Grubert,1,2,* Christopher Heffelfinger,1 Manoj Hariharan,1,2 Akwasi Asabere,1 Sebastian M. Waszak,3, 4 Lukas Habegger,5 Joel Rozowsky,6 Minyi Shi,1,2 Alexander E. Urban,1, 7 Mi-Young Hong,1 Konrad J. Karczewski,2 Wolfgang Huber,3 Sherman M. Weissman,7 Mark B. Gerstein,5,6,8 Jan O. Korbel,3, 9, Michael Snyder1,6,7,
Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee using chromatin immunoprecipitation followed by sequencing (ChIP-Seq). The binding sites of RNA Polymerase II (PolII) and a key regulator of immune responses, NFB (p65), were mapped in ten lymphoblastoid cell lines and 25% and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with SNPs and genomic structural variants (SVs) and were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between human and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding and provide insight into the genetic events responsible for these differences.
Nature doi:10.1038/nature08934
Genetic analysis of variation in transcription factor binding in yeast
Wei Zheng1,6, Hongyu Zhao2,3, Eugenio Mancera4, Lars M. Steinmetz4 & Michael Snyder1,5
Department of Molecular, Cellular and Developmental Biology, Yale University,
Program in Computational Biology and Bioinformatics, Yale University,
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
Present address: Biostatics Resources, Keck Laboratory, Yale University, New Haven, Connecticut 06520, USA.