Genetics and epigenetics of centromeres
Centromeres, referred to as the black hole of our genome, are chromosomal regions that attach to spindle fibers to facilitate chromosome segregation. Centromere defects lead to aneuploidies that are a common cause of miscarriages and a hallmark of the majority of cancers. We have a longstanding interest in understanding how centromeres are specified. Despite their indispensable role in chromosome segregation, centromeric sequences between closely related species are not conserved. In the absence of conserved DNA elements, what determines centromere sites on a chromosome, remains unknown. The key to understanding centromere specification lies in the specialized epigenetic chromatin assembled on centromeres. Our primary focus is to investigate how centromeric chromatin is established and maintained in different mammalian species using genomics, genetics, cell biology, and occasionally evolutionary biology-based approaches.
Role of RNA in chromatin organization
We are also interested in understanding the structural organization of distinct chromatin domains in the nucleus. Besides chromatin modifier proteins, chromatin is also associated with a significant fraction of mature transcripts, mostly long non-coding RNAs. The ability of RNA to form multivalent interactions via its sequence and extensive secondary structures makes it an excellent modifier of chromatin structure. Emerging evidence suggest that chromatin-associated RNA is indeed involved in chromatin organization. To understand how lncRNAs modify chromatin structure, we are investigating chromatin-RNA interactions using the latest chromatin profiling techniques combined with cytological visualization.