A Domain Constrained Principal Component Analysis of ChIP-Seq Data Reveals Significant Association between Transcription Factors and Histone Marks in Mouse Embryonic Stem Cells

• Main Authors: Tseng, Chin-Wen, 曾晴雯
• Other Authors: Hung, Jui-Hung
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/m59y8x

碩士 === 國立交通大學 === 生物資訊及系統生物研究所 === 103 === The meta-analysis based on genome-wide profiles of transcription factor binding, nucleosome occupancy, and epigenetic marks is one of the powerful approaches to understand the complex regulatory circuitry in a large scale. Sophisticated regulation in the level of epigenetics reveals selective binding or chromatin state switching located on enhancers, transposons, pseudogenes, lncRNAs, and so on, which in part explains the machinery of underlying biological processes. We developed a computational framework that efficiently reveals profiles that show similar characteristics on a high-dimensional domain with biological knowledge constraints. We applied this framework to investigate ChIP-seq data from ENCODE and successfully clustered enhance related factors. By looking into those clusters, we found Ash2l and Oct4 co-localize on some enhancer regions and further by applying in-depth analysis and wet-lab experiments, we verified that Ash2l and Oct4 co-localize on an enhancer region distant to a stemness gene Nanog and their binding indeed enhances the expression of Nanog.