Research in the lab
Our work focuses on the formation and regulation of chromatin domains and their ultimate roles in the nucleus. We are particularly interested in the mechanisms of heterochromatin establishment and function. Heterochromatin operates in organisms from yeast to humans to determine cell identity and maintain genome stability by silencing genes. Because heterochromatin functions in such central processes, misregulation of this genomic structure can have dire consequences such as cancer or abnormal development. Our work investigates the mechanisms by which silencing is carried out. We use a combination of in vitro assembly of chromatin domains, mechanistic biochemistry, proteomic analysis, and genome-wide chromatin profiling to understand the complex superstructural “neighborhoods” of chromosomes.
Two main projects drive our studies:
1) Using budding yeast heterochromatin as a model to comprehensively characterize a specific chromatin domain. The genetics of budding yeast chromatin-mediated gene silencing have provided an extensive foundation for understanding chromatin biology in all eukaryotes. The next step for this model is to provide new insights through biochemistry. We have demonstrated that a functional yeast heterochromatin domain can be assembled in the test tube, which opens up many doors to characterize the mechanism. Projects include:
- Detailed biochemical analysis on the interplay between RNA Polymerase II and silencing factors.
- Understanding the mechanism of directional spreading of the silencing structure along a chromatin fiber.
- How heterochromatin is re-established in an epigenetic pattern.
- Comprehensive characterization of the yeast heterochromatin interactome using quantitative proteomics.
2) Mechanisms of long noncoding RNA-mediated silencing. We aim to understand how RNA can contribute to specificity in triggering formation of a transcriptionally repressed chromatin domain.