在9月26日的《美國科學(xué)院院刊》雜志上，來自耶魯大學(xué)的華裔學(xué)者俞海源（Haiyuan Yu,，分子生物物理和生物化學(xué)博士后）和同事Mark Gerstein公布了他們對基因調(diào)節(jié)網(wǎng)絡(luò)分級結(jié)構(gòu)的基因組分析結(jié)果。
生物學(xué)中的一個基礎(chǔ)問題就是細(xì)胞如何根據(jù)不同的刺激,，利用轉(zhuǎn)錄因子來協(xié)調(diào)成千上萬個基因的表達(dá),。轉(zhuǎn)錄因子和它們的靶標(biāo)基因之間的關(guān)系能夠根據(jù)定向調(diào)節(jié)網(wǎng)絡(luò)被模擬出來。這些關(guān)系與社會網(wǎng)絡(luò)中的“指令鏈”結(jié)構(gòu)類似,，這種結(jié)構(gòu)的特點是具有分級層次特征,。
在這項新的研究中，俞博士和同事研究出了確定普遍化的層次的運(yùn)算方法,，并且利用這些方法闡明了存在俞典型原核生物（大腸桿菌）和真核生物（酵母）的調(diào)節(jié)網(wǎng)絡(luò)中的廣泛的金字塔形層次結(jié)構(gòu)——大部分轉(zhuǎn)錄因子處于金字塔底部,，只有少數(shù)轉(zhuǎn)錄因子處于頂部。
這些處于頂部的主控因子處于蛋白質(zhì)－蛋白質(zhì)相互作用網(wǎng)絡(luò)的中央,，它們能夠通過蛋白質(zhì)相互作用接受來自整個調(diào)節(jié)層次的信息輸入,。而且，它們還對其他基因具有最大的影響力,。但是,，令人驚訝的是，處于調(diào)節(jié)層次底部的轉(zhuǎn)錄因子對細(xì)胞的生存更為重要,。
研究人員曾經(jīng)認(rèn)為主控轉(zhuǎn)錄因子通過直接調(diào)節(jié)許多基因來產(chǎn)生廣泛的影響,，但事實上具有最多直接的調(diào)節(jié)靶標(biāo)的轉(zhuǎn)錄因子處于這種層次網(wǎng)絡(luò)的中間。俞博士發(fā)現(xiàn)這些中等轉(zhuǎn)錄因子是整個層次網(wǎng)絡(luò)的“控制瓶頸”,，這種中級管理者的控制程度與不同企業(yè)和政府機(jī)構(gòu)中的社會結(jié)構(gòu)非常相似,。
在這項研究中，俞博士和M. G.共同完成了實驗設(shè)計,，俞博士進(jìn)行了實驗并完成資料分析,。
原始出處：
Haiyuan Yu and Mark Gerstein
Genomic analysis of the hierarchical structure of regulatory networks
PNAS published September 26, 2006, 10.1073/pnas.0508637103 [Abstract] [PDF] [Supporting Information]
A fundamental question in biology is how the cell uses transcription factors (TFs) to coordinate the expression of thousands of genes in response to various stimuli. The relationships between TFs and their target genes can be modeled in terms of directed regulatory networks. These relationships, in turn, can be readily compared with commonplace "chain-of-command" structures in social networks, which have characteristic hierarchical layouts. Here, we develop algorithms for identifying generalized hierarchies (allowing for various loop structures) and use these approaches to illuminate extensive pyramid-shaped hierarchical structures existing in the regulatory networks of representative prokaryotes (Escherichia coli) and eukaryotes (Saccharomyces cerevisiae), with most TFs at the bottom levels and only a few master TFs on top. These masters are situated near the center of the protein-protein interaction network, a different type of network from the regulatory one, and they receive most of the input for the whole regulatory hierarchy through protein interactions. Moreover, they have maximal influence over other genes, in terms of affecting expression-level changes. Surprisingly, however, TFs at the bottom of the regulatory hierarchy are more essential to the viability of the cell. Finally, one might think master TFs achieve their wide influence through directly regulating many targets, but TFs with most direct targets are in the middle of the hierarchy. We find, in fact, that these midlevel TFs are "control bottlenecks" in the hierarchy, and this great degree of control for "middle managers" has parallels in efficient social structures in various corporate and governmental settings.
