Chromatin (most studies performed in fission yeast, S. pombe)

• How does histone H3 lysine 9 methylation trigger heterochromatin formation?
• How are boundaries formed between euchromatin and heterochromatin?
• How do noncoding RNAs trigger the formation of repressive chromatin?

Why these questions interest us: The packaging of DNA into repressive heterochromatin is linked to the formation of specialized domains of eukaryotic chromosomes:  in particular, centromeres and telomeres. Pericentromeric heterochromatin is particularly important because it is involved in specifying the location of centromeres. In many systems, it is clear that heterochromatin initiates at specific sites, spreads along the DNA fiber, appears to be inherited in cis, and that its extent is tightly regulated. Even more intriguing is the finding that in many systems, noncoding RNAs play a role in directing the formation of heterochromatin. The mechanistic foundation for all of these activities remains obscure, yet they are critical for the functioning of euchromatic chromosomes. In addition, it is clear that the formation of ectopic repressive chromatin promotes the silencing of tumor suppressor genes in human cancer as well as in the genesis of drug resistance in tumors. Thus an understanding of how repressive chromatin is regulated represents a major unsolved question relevant to both normal biology and disease.

Our progress in this area as well previous studies on euchromatin can be found in our publications on chromatin biology: click here.