真核基因转录调控的协同机制研究及理论模型

A simplified biochemical system was set up to study the mechanism of transcriptional synergy from multiple binding sites upstream of genes. A mathematical model was developed and by comparing the model to the transcriptional response from a DNA template sequence bearing repeated upstream binding sites, it was found that the multiple binding sites constitute a precise and efficient switch for the regulatory control of gene transcription. This result led to the analysis on the distribution of transcription regulating sites (TRS) over genomes to figure out how these multiple sites combine together to form a functional switch signal for the transcriptional activation. A statistical model employing nucleotide frequency and TRS distributional frequency over the whole genomes was introduced to measure the enrichment of TRS in different classes of genomic sequences as well as the distribution pattern of TRS over some genomes.

本课题拟以调控蛋白ZEBRA激活EBV病毒溶胞周期的转录为实验体系，系统研究调控蛋白浓度、上游调控蛋白结合位点数目、分布和结合强度等因素对转录的调控作用，创建多位点多级生化反应系统的协同作用模型，描述各种调控因素对系统转录水平的精确调控关系，阐明真核基因转录的调控机理，为探索细胞分化发育等生物学基本问题奠定基础。