Principle Investigator: Matthew Weirauch, Phd

Matthew Weirauch, Cincinnati Children's.Gene regulation is the fundamental process that controls the precise spatiotemporal control of gene expression in all cell types within all organisms. With the discovery that about 90 percent of disease-associated genetic variants reside within likely regulatory regions, gene regulation is now considered to be a key player in the mechanistic action of many human diseases. The process of gene regulation is largely controlled by transcription factors (TFs), proteins that enable the activation or repression of gene expression after recognition of short genomic DNA sequence “motifs.” According to our latest estimates, the more than 700 currently sequenced eukaryotic genomes contain more than 400,000 TFs.

Recent efforts spearheaded by my group aim to systematically measure and computationally infer the motifs of all TFs. This unprecedented initiative provides data of fundamental importance to virtually any genomic analysis in any organism. We have similar initiatives underway for RNA binding proteins (RBPs), which bind RNA and control post-transcriptional processes, such as splicing, mRNA stability, and mRNA localization. To house these data, we created the CisBP and CisBP-RNA databases, comprehensive resources used by thousands of researchers across the world. Since their births a few years ago, we have learned much about gene regulatory mechanisms, and many new exciting technologies have emerged. We propose to extend our databases with improved models, new tools, and new datasets.