Bioinformatic analysis of changes in RNA polymerase II transcription stimulated by estradiol in MCF7 cells

 Jie Wu, Yan Cai, Gaiping Zhao

Abstract:

Estradiol (E2) is the most potent estrogen and RNA polymerase II (Pol II) regulates a great mass of gene expression. This study was designed to illustrate the mechanisms of estrogen-dependent human breast cancer (BC) through Pol II. ChIP-seq data, DNase-seq data and other sequencing data of human BC MCF-7 cells were downloaded from Gene Expression Omnibus database. Each of these datasets included one control and one E2 treated samples. Sequence alignment was performed and Pol II factor binding signal was determined. Functional enrichment analysis of particular genes was performed, along with transcription factor (TF) motif enrichment analysis. Sites with enhanced Pol II binding were identified in intergenic regions. Pol II binding sites with increased binding signal facilitated chromosome switching from a closed to an open state. A total of 59 TFs, including KLF4 (Kruppel-like factor 4), were identified. Besides, Enrichment analysis revealed that protein synthesis and metabolic processes as well as cell cycle processes were highlighted. The KLF4 motif was found to be enriched and was significantly enhanced in the promoter region for Pol II binding. Cell cycle processes, protein synthesis and metabolism play critical roles in the progression of E2-stimulated BC. In addition, KLF4 may be important for the progression.