Gene expression is regulated at many levels. Regulation at the level of transcriptional initiation has been extensively studied, and at the heart of this process lie transcriptional factors (TFs). The existing paradigm holds that TFs act by binding in a sequence-specific manner to regulatory elements on DNA and control the expression of the target gene. Our genome encodes ~1800 predicted TFs. However, despite the advent of large scale datasets, we do not have biochemical or functional data for the majority of these TFs. A recent large-scale high-throughput study could determine an in vitro binding motif for only ~25% of human TFs.  

Emerging data also reveal that some TFs can bind RNA and regulate gene expression at the post-transcriptional level. This suggests that RNA binding might constitute an important, yet unexplored, activity of many TFs. Currently, the possible RNA-binding activity of human TFs has been addressed for less than ~0.5% of human TFs.

We seek to discover whether RNA-binding activity is pervasive and functionally relevant among human TFs. In the first instance, we will use high-throughput protein arrays to assess the RNA-binding capacity of human TFs. Subsequently, we will obtain detailed binding specificities for each TF using the Bind-n-seq protocol.

If our hypothesis proves to be correct, a new dimension will be opened up in our understanding of gene regulation and our data will serve as the foundation from which a broad range of functional and structural analyses will arise.