酵母核糖体蛋白基因组合转录调控位点统计分析

Statistical analysis of combinatorial transcription regulation sites in ribosomal protein genes of yeast

真核基因的转录调控是后基因组时代研究的主要问题之一,其基础是认识DNA上转录因子结合位点(模体)及分布状况。基于马尔可夫链模型对酵母核糖体蛋白基因上游启动子序列中模体出现次数进行统计,利用Z-score统计量抽提出过表达和低表达的模体,其中95%的模体与实验得到的转录因子结合位点相符合。然后将抽提出的模体两两配对,通过与背景序列比较,找出酵母核糖体蛋白基因中出现概率及距离分布均具有统计显著性的模体对,这些非随机出现的模体对具有潜在的组合转录调控功能,其中一些模体对的组合调控作用已有实验支持。对提取出的模体对在序列中的位置分布进行分析,发现近94%的模体对位于转录起始位点上游,超过半数的模体对两模体之间的最短距离在0～100bp之间,距离小于30bp的模体对接近30%,这样的短距离间隔有利于两模体的相同作用。这些结果将有助于对酵母核糖体蛋白基因转录调控机制的深入认识。

The transcriptional regulation of eukaryotic genes is one of the major problems in the post - genomics era. The preliminary work is to identify the transcription factor binding sites （motifs） and their distributions in DNA. In this paper, we first counted the oc- currence numbers of the motifs in the upstream promoter sequences of the ribosomal protein （RP） genes of Saccharomyces cerevisiae yeast based on Markov chain model. Then some over - and under - represented motifs were extracted by using a Z - score statistic. 95% of these motifs are accordance with the transcription factor binding sites which are verified by experimental analyses. Pairing the above motifs each other and comparing to a set of background sequences, we detected some motif pairs with statistical significance both on occurrence numbers and on distance distributions in the RP genes of yeast. Combinatorial transcription regulation probably takes place for every these non - random motif pairs. The combinatorial regulations of some of these motif pairs have been verified by labora- tory work. Checking the positions of the motif pairs, it was found that about 94% of the motif pairs are located upstream to transcription start sites （TSS）. For an overwhelming majority of the motif pairs, the distances between each two motifs are less than 100bp, and 30% of them are less than 30bp. Such a small space of a motif pair may be favorable for the interaction of the two motifs. These results will be helpful for understanding the mechanisms of the transcriptional regulation for RP genes in yeast.