William Park

Professor | Biochemistry & Biophysics

mediator complex, gene regulation, regulatory evolution, ethanol tolerance, yeast genetics, structure/function tuning

Office:BICH / 214

The primary goals of our current research are to understand how the mediator complex integrates genetic information to regulate transcription and how altering the structure of the mediator complex modulates its input/output properties. Most of my lab’s work over the last twenty-five years has focused on manipulating starch biosynthesis to improve rice’s nutritional quality. The majority of this work was proprietary and thus not published, but it is represented by several popular products currently on grocery store shelves in the U.S., Europe, and Australia.

Mediator complex

Structure 5OQM of the mediator complex, indicating the region of Med8 that is important for ethanol tolerance in yeast.
See Nature 51, 204–209 (2017).

The mediator complex plays a key role in transcription in all eukaryotes and is often described as a “processor” of genetic information. However, little is known about how the mediator complex integrates inputs from multiple transcription factors and other signal transduction pathways to control the expression of specific genes and gene sets. Considering its key central role in gene expression, some aspects of mediator signal processing must be highly conserved. More importantly, other aspects of signal integration must differ between organisms with different physiological needs. Altering the mediator complex structure provides a way to modulate how it integrates signals and, thus, its input/output properties. Since the mediator coordinately regulates thousands of genes, mediator mutations would be expected to alter the expression of large numbers of genes. However, for the mediator complex to have been able to evolve to meet the needs of divergent organisms, such changes must have a significant chance of being physiologically workable – either directly or via compensation by second-site mutations.

We are currently looking at mediator sequences involved in S. cerevisiae’s ability to produce and tolerate high concentrations of ethanol. These are traits of commercial importance but are also interesting examples of the multi-step evolution of new metabolic capability. Recently, we identified a short region near the CTD binding domain of the mediator complex required for ethanol tolerance but has little effect on media without ethanol. This region likely plays a key role in gene and context-specific changes in the mediator complex’s structure and activity in response to ethanol. It provides an experimentally amenable system to examine how mediator structure and conformation regulate gene expression and how mediator structure/function relationships change during evolution.

B. L. Allen and D. J. Taatjes, The mediator complex: a central integrator of transcription. Nat. Rev. Mol. Cell Biol. 16, 155–16 (2015).

Z. C. Poss, C. C. Ebmeier, D. J. Taatjes, The mediator complex and transcription regulation. Crit. Rev. Biochem. Mol. Biol. 48, 575–608 (2013).