Grant: CIHR Fellowship

Heterochromatin is densely packed DNA that is transcriptionally silenced and no longer expressed. The maintenance and formation of heterochromatin is immensely important in cell identity and often misregulated in many diseases. Post-translational modifications (PTMs) are often small dynamic changes made to proteins that can have broad implications on their function. H3K9me3 is one particular PTM known to cause heterochromatin formation through its recognition by H3K9me3 reader proteins. The enzymes required to convert H3K9me1 to H3K9me3 play a key role in heterochromatin formation. However when H3K9me3 is biochemically diminished to H3K9me1, heterochromatic regions are maintained. This work suggests that H3K9me1 may have a more important role in heterochromatin formation than originally postulated. However the mechanisms behind H3K9me1 recognition are poorly understood, which hampers our basic understanding of the pathway. I propose to identify novel H3K9me1 reader proteins and study their cellular roles as well as fully characterize the H3K9me1 mark genome-wide. Lastly, I will develop inhibitors of the H3K9me1 reader protein interaction to probe its cellular importance with respect to changes in heterochromatin formation. A better understanding of H3K9me1 and its associated proteins will provide insight into heterochromatin formation, a basic cellular phenomenon. This research is of great importance to the field of molecular and cellular biology and epigenetics. Epigenetics is a relatively new field that is gaining significant scientific interest due to the potential to develop medical treatments for a range of diseases. Researchers, like me, are desperately needed to fully explore the scientific and societal benefits that may be realized by a better understanding of basic epigenetic processes. During my postdoctoral research I will gain expertise to bring back to Canada to strengthen Canada's role as an international leader in scientific research.