Summary
This research project aims to decipher the role of heterochromatin, specifically the H3K9me3 histone mark, in telomere function and maintenance mechanisms, including its impact on genome stability, replicative aging, senescence, and the alternative lengthening of telomeres (ALT) mechanism.
What they want
The project will employ a novel approach to locally and specifically modulate histone methylation at telomeres by fusing histone modifying enzymes to the shelterin protein TRF1. This method will be used to thoroughly dissect the function of H3K9me3 in telomere protection (end-protection, end-replication, entry into senescence) and its influence on the ALT mechanism of telomere maintenance. Preliminary data indicate that loss of H3K9me3 leads to replication defects and de-repression of telomere transcription, and that H3K9me3 drives ALT activity.
Deliverables
- Methodical determination of the function of H3K9 trimethylation on the protective properties of telomeres (end-protection, end-replication, entry into senescence)
- Methodical determination of the function of H3K9 trimethylation on the ALT mechanism of telomere maintenance
