基因調(diào)節(jié)網(wǎng)絡包括轉(zhuǎn)錄調(diào)節(jié)（transcriptional regulation）,、信號傳導（signal transduction）和染色體重塑（chromatin modification）。序列多樣性（Sequence polymorphisms）通過影響復雜的基因調(diào)節(jié)網(wǎng)絡（regulatory network）影響基因表達,。斯坦福大學研究人員Su-In Lee等利用一種叫做Geronemo的方法,，直接尋找遺傳改變影響調(diào)節(jié)網(wǎng)絡的機制,。文章刊登于2006年9月12日PNAS電子版。
Geronemo自發(fā)設計出一系列協(xié)同基因（coregulated genes 生物通編者譯）或稱modules（模數(shù)）,。這些模數(shù)的改變能夠引發(fā)基因改變和調(diào)節(jié)劑的表達,。Geronemo通過利用基因序列調(diào)節(jié)系統(tǒng)的模塊性，能夠在一些一直被認為是無關的基因之間找到調(diào)節(jié)相關性（regulatory relationships）,，有助于發(fā)現(xiàn)復雜的基因調(diào)節(jié)網(wǎng)絡機制,。Geronemo將基因型調(diào)節(jié)物和表達調(diào)節(jié)物結合考慮，為一些沒有直接作用于靶標的序列變異性（sequence variation）捕捉到了結果,。
研究人員將實驗室培養(yǎng)的BY4716 (BY)啤酒酵母（Saccharomyces cerevisiae.）菌株和野生型RM11-1a (RM) 啤酒酵母菌株雜交,，得到雜交后代。利用Geronemo分析雜交后代的資料,，推測出一系列從未描述過的有關酵母調(diào)節(jié)網(wǎng)絡遺傳機制變化的假說。包括轉(zhuǎn)錄調(diào)節(jié)（transcriptional regulation）,、信號傳導（signal transduction）和染色體重塑（chromatin modification）,。研究人員發(fā)現(xiàn)，大量的模數(shù)具有染色體特征,，而且能夠被染色體重塑蛋白調(diào)節(jié),。事實上,，表達中的許多發(fā)生變化的小片段可以用一小部分與染色體重塑有關的標記來解釋。附加的分析顯示,，Swi/Snf染色體重塑復合體的序列進化（sequence evolution）是正向選擇的結果,。
研究人員總結認為，酵母進化過程中存在的個體表達差異,，一部分原因是小數(shù)量染色體結構重塑,。
部分英文原文：
Identifying regulatory mechanisms using individual variation reveals key role for chromatin modification
Sequence polymorphisms affect gene expression by perturbing the complex network of regulatory interactions. We propose a probabilistic method, called Geronemo, which directly aims to identify the mechanism by which genetic changes perturb the regulatory network. Geronemo automatically constructs a set of coregulated genes (modules), whose regulation can involve both sequence variations and expression of regulators. By exploiting the modularity of genetic regulatory systems, Geronemo reveals regulatory relationships that are indiscernible when genes are considered in isolation, allowing the recovery of intricate combinatorial regulation. By incorporating both expression and genotype of regulators, Geronemo captures cases where the effect of sequence variation on its targets is indirect. We applied Geronemo to a data set from the progeny generated by a cross between laboratory BY4716 (BY) and wild RM11-1a (RM) isolates of Saccharomyces cerevisiae. Geronemo produced previously undescribed hypotheses regarding genetic perturbations in the yeast regulatory network, including transcriptional regulation, signal transduction, and chromatin modification. In particular, we find a large number of modules that have both chromosomal characteristics and are regulated by chromatin modification proteins. Indeed, a large fraction of the variance in the expression can be explained by a small number of markers associated with chromatin modifiers. Additional analysis reveals positive selection for sequence evolution of elements in the Swi/Snf chromatin remodeling complex. Overall, our results suggest that a significant part of individual expression variation in yeast arises from evolution of a small number of chromatin structure modifiers.
