眾多序列特異的轉(zhuǎn)錄因子 （transcription factors ，TFs） 組合而成交叉的調(diào)控網(wǎng)絡(luò),，這些調(diào)控網(wǎng)絡(luò)構(gòu)成細(xì)胞發(fā)揮生物學(xué)功能的基礎(chǔ)。
9月5日，國際著名雜志Cell在線發(fā)表了美國華盛頓大學(xué)等科研人員的一篇題為Circuitry and Dynamics of Human Transcription Factor Regulatory Networks的研究論文,，報(bào)道了人轉(zhuǎn)錄因子調(diào)控網(wǎng)絡(luò)環(huán)路，動力學(xué)和組織原理,。
研究人員采用全基因的體內(nèi)DNaseI 足跡法,，在41種不同的細(xì)胞和組織中找到了475個序列特異的轉(zhuǎn)錄因子間的聯(lián)系 ，然后分析這些聯(lián)系的動力學(xué),。
研究發(fā)現(xiàn)人轉(zhuǎn)錄因子網(wǎng)絡(luò)具有高度的細(xì)胞選擇性,，細(xì)胞選擇性由數(shù)種因子驅(qū)動，其中包括在控制細(xì)胞身份中未被識別的調(diào)節(jié)子,。而且,，還鑒定出多種影響轉(zhuǎn)錄調(diào)控網(wǎng)絡(luò)的廣泛表達(dá)的因子。
令人震驚的是,，盡管轉(zhuǎn)錄因子內(nèi)在的多樣性,，所有細(xì)胞類型的調(diào)控網(wǎng)絡(luò)各自獨(dú)立地匯聚到一起，如同生命體的神經(jīng)網(wǎng)絡(luò),。
本研究提供了人轉(zhuǎn)錄因子調(diào)控網(wǎng)絡(luò)環(huán)路,，動力學(xué)和組織原理等的廣泛描述。（生物谷Bioon.com）
doi:10.1016/j.cell.2012.04.040
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Circuitry and Dynamics of Human Transcription Factor Regulatory Networks
Shane Neph, Andrew B. Stergachis, Alex Reynolds, Richard Sandstrom, Elhanan Borenstein, John A. Stamatoyannopoulos
The combinatorial cross-regulation of hundreds of sequence-specific transcription factors (TFs) defines a regulatory network that underlies cellular identity and function. Here we use genome-wide maps of in vivo DNaseI footprints to assemble an extensive core human regulatory network comprising connections among 475 sequence-specific TFs and to analyze the dynamics of these connections across 41 diverse cell and tissue types. We find that human TF networks are highly cell selective and are driven by cohorts of factors that include regulators with previously unrecognized roles in control of cellular identity. Moreover, we identify many widely expressed factors that impact transcriptional regulatory networks in a cell-selective manner. Strikingly, in spite of their inherent diversity, all cell-type regulatory networks independently converge on a common architecture that closely resembles the topology of living neuronal networks. Together, our results provide an extensive description of the circuitry, dynamics, and organizing principles of the human TF regulatory network.
