The Role of Transcription Factors in Determining Alternative Polyadenylation

Alternative polyadenylation is a widespread mechanism of gene regulation in which the RNA polymerase II generates alternative 3' end transcripts. It is a tissue-specific phenomenon that is regulated globally depending on extracellular signals as well as internal ones related to cell proliferation and differentiation. Previous studies have analyzed the genetic determinants of alternative polyadenylation, as well as gene expression and transcript structure, to discover the mechanisms of action of these variants. The purpose of my work was to use enrichment analysis using Position Weight Matrix (PWM), as well as a Stratified LD Score Regression (S-LDSC) on ChIP-seq data, to analyze the role of transcription factor binding in explaining the genetic determinants of alternative polyadenylation. We found the enrichment of 307 transcription factors with the PWM analysis and the enrichment of 71 using the S-LDSC, with 13 transcription factors in common between the two results. These findings show that indeed transcription factor binding appears to be an important element in determining alternative polyadenylation and suggest that new experimental research in this direction could lead to a better understanding of the regulatory network of alternative polyadenylation.