Research

Partial, Poised, Paused PIC

Summary

CEGR research is aimed at understanding how eukaryotic genes are regulated at a molecular level. Our physical location within shared space maximizes interactions that promote innovative thinking. Each lab brings unique strengths that together achieve a level of synergy that is rarely matched in scientific research. This includes excellence in biochemical assembly mechanisms in chromatin and transcription. It includes methods X-ray crystallography, cryo-EM, and a variety of biophysical methods to elucidate the structure and mechanism by which proteins interact with nucleosomes. We aim to understand how the bizarre repetitive structure of RNA polymerase II C-terminal domain regulates the transcription cycle. As we all know, specificity in gene regulation boils down to proteins selectively recognizing specific features (sequence and shape) on DNA, as allowed by the chromatin landscape, then using these anchor points to coelsce transcription complex assembly. We have developed state-of-the-art concepts about how DNA binding proteins access DNA that is encased in chromatin. We are studying how this gives rise to cell-type specific gene expression, for example, in making motor neurons or red blood cells. Through our experiments on human and mouse model systems we develop concepts about transcriptional regulation goes awry in cancer, and how we might use this knowledge to develop rectifying therapeutic drugs.