Analysis And Functional Study Of Transcription Regulatory Elements In Bidirectional Promoter

Bidirectional promoters are shared promoter sequences between divergentgene pair (genes proximal to each other on opposite strands), and can regulate thegenes in both directions. In the human genome,>10%of protein-coding genes arearranged head-to-head on opposite strands, with transcription start sites that areseparated by <1,000base pairs. Many transcription factor binding sites occur inthe bidirectional promoters that influence the expression of2opposite genes.Recently, RNA polymerase II (RPol II) ChIP-seq data are used to identify thepromoters of coding genes and non-coding RNAs. However, a bidirectionalpromoter with RPol II ChIP-Seq data in different cell lines has not been found. Inthis thesis, we incorporated different types of ENCODE data in the process of theidentification of regulatory regions in bidirectional promoter. Furthermore weanalyzed the influence of multiple transcription factors and DNA methylation onthe types of bidirectional promoters. The major contents of this thesis include thefollowing parts:(1) A method based on NGS data in ENCODE project to identify regulatoryregions in bidirectional promoters is presented.The identification of promoter regions has always been an important topic inthe research of gene transcription. ENCODE project provides different types ofdata to support further research in this area. Due to the fact that RNA polymeraseII ChIP-seq data has a clear peak near transcription start sites, we designed amodel of RNA Pol II’s distribution near bidirectional promoters and furtherpresented a PSO-based algorithm for parameter optimization. we successfullyidentified regulatory regions of bidirectional promoters in51samples of16celllines. In addition, we extracted the features to classify bidirectional promoters andthen put them into4categories.(2) Analysis on multiple transcription factors affinity to bidirectionalpromoters.Transcription factors(TFs) play significant roles in the transcription process.We studied the binding profile of60different transcription factors in the Hela-S3cell line. We analyzed the affinity of single TF to regulatory regions and itsinfluence on the types of bidirectional promoters. Furthermore, we used Apriorialgorithm to analyze the association of different TFs.(3) Analysis on the influence of DNA methylation on bidirectional promoters.DNA methylation plays an important role on the epigenetic level. In this thesis, we used high throughput data of DNA methylation to analyze its influence onbidirectional promoters.