Allshire Lab Profile

Research Focus: RNA Interference, Silent Chromatin and Centromere Integrity

In fungal, plant and animal systems it is clear that non-coding RNAs play key roles in mediating the formation of silent chromatin. The expression of exogenous double stranded RNA homologous to a target gene can induce DNA methylation and histone H3 lysine 9 methylation and gene silencing. Double stranded RNAs are processed by the RNA interference machinery to produce short interfering siRNAs that somehow home in on homologous chromatin and induce the assembly of silent chromatin. In fission yeast endogenous non-coding transcripts are produced from centromere associated repeats and the resulting homologous siRNA allow the formation of centromeric heterochromatin over these repeats. This silent chromatin is required to mediate tight physical cohesion between sister-centromeres by maintaing a high density of cohesin on these centromere repeats. RNAi and silent chromatin components are therefore for normal chromosome segregation during mitosis and their disruption results defective centromere function.

The centromere specific histone H3 like protein CENP-A is a fundamental component in specifying the site of centromere assembly in most eukaryotes. CENP-A replaces normal histone H3 specifically at active centromeres and its incorporation and propagation at a particular site is subject to epigenetic regulation. How CENP-A is deposited and maintained only at active is not known but understanding this process is fundamental to dissecting the process of kinetochore assembly.