Currently, the Tsai lab is especially interested in these two directions:
1. Structural and functional studies of the eukaryotic transcription complexes
The human 1.5 MDa transcriptional Mediator complex, consisting of 25 core Mediator proteins and a dissociable CDK8 kinase module, plays an essential role in transcriptional regulation by conveying regulatory signals to the RNA polymerase II (Pol II) transcription machinery. While the molecular mechanism by which Mediator regulates transcription has not been entirely elucidated; its dysfunction and dysregulation have been extensively linked to a variety of human diseases, including cancer. Recently, we successfully determined the core Mediator structure at near-atomic resolution (Figure 1), revealing the molecular interactions between core Mediator and Pol II during transcription initiation (Published in Cell 2014 and Nature 2017). Our near-term goals are to 1)explore the molecular mechanism underlying Mediator regulation by IncRNA and 2) identify new IncRNAs potentially linked to diseases through interactions with Mediator.
2. Macromolecular complexes involved in regulation of 3D genome architecture
In the cells, the structure of the 3D genome influences gene regulation, evolution, and cell fate decisions. How chromatin is organized within the nucleus and how genome architecture is regulated and maintained are important emerging biological questions. To regulate genome architecture, numerous protein complexes are involved in this process. We will use various structural and molecular approaches to study the structures and molecular mechanisms of the complexes involved in the regulation of genome architecture.
Mediator, transcription, gene regulation, epigentics, cancer, nucleosome, chromatin remodeling, long noncoding RNA (IncRNA), 3D genome architecture, structure, X-ray crystallography, and cryo-EM.