Project P03

About

Gene expression is initiated via transcription factors (TFs) binding chromatin, before RNA-binding proteins (RBPs) engage on nascent RNA. However, there are recent examples of TFs that also bind RNA in a regulatory manner. What remains unclear is how such dual association with RNA and DNA controls gene expression. To address this, we will use senescence of human cells as a model for identifying and mechanistically dissecting the roles of chromatin-binding TFs that are also bona fide RBPs. We curated a list of 66 TFs that qualify as RBPs, are differentially regulated in two senescence models, and can affect RNA processing and 3D genome conformation. From these, we will focus on HMGB2 and AHCTF1 and combine genome-edited lines allowing for the acute and controllable degradation of each factor with genomics, super-resolution imaging, and functional assays to dissect their roles on chromatin versus those on RNA.