The Full Story
Tsai lab
Our laboratory is interested in understanding the molecular mechanism and structure of macromolecular machines, such as coactivators, chromatin remodeling complexes, and long non-coding RNA molecules (lncRNAs), which are involved in human diseases caused by abnormal gene regulation. Recent development in cryo-electron microscopy (cryo-EM) has already made it possible to determine the structure of the macromolecular complex at near-atomic resolution. We combine the advanced cryo-EM techniques with various biochemical and biophysical approaches to explore the structure and biological function of these macromolecular assemblies.
The eukaryotic transcriptional Mediator complex
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 transcription machinery. While the molecular mechanism by which Mediator regulates transcription has not been entirely elucidated. Our near-term goals are to 1) explore the molecular mechanism underlying Mediator regulation and 2) identify new lncRNAs or proteins potentially linked to human diseases through interactions with the Mediator complex.
Uterine leiomyoma
Our cryo–electron microscopy structure of Saccharomyces cerevisiae CKM explains the mechanism of Med12-dependent Cdk8 activation and provide a novel potential drug target for uterine leiomyoma.
Hypoxia
HIF2A contributes to cardioprotection during myocardial IR injury. We tried to investigate the transcription machinery by using biochemical and biophysical tools.