Studying RNA transcription regulation via RNA-binding proteins
DRBP are proteins capable of binding DNA and RNA. Due to their dual capacity, those proteins can act at different steps of the gene expression pathway. Recent studies employing ChIP-seq have shown that several RNA-binding proteins (RBPs) bind chromatin at the promoter region, suggesting a relationship between RBPs and transcription regulation. However, only a few overlaps were shown between the binding sites of the RBPs on DNA and on RNA. The aim of my thesis is to explore RNA binding protein interactions with chromatin via transcription factors. We first employed an experimental approach, using the CUT&RUN technique on SRSF1, a splicing factor that belongs to the human SR family protein. We show that in human embryonic stem cells, SRSF1 binds DNA, preferably at gene promoter regions, in a sequence specific manner. We found that the preferred binding motif of SRSF1 resembles the binding motif of the NFY transcription factor (TF) family, suggesting that it binds the DNA through TF interaction. We further employed a computational approach for exploring the binding preferences of other RBPs on the DNA We further developed a motif search approach and a position-based approach for predicting putative interactions between RBPs and TFs and applied it on publicly available high throughput binding data from human K562 cells.
