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Targeting PcG complexes at bivalent genes.
Ailbhe Brazel, Irene Kallimasioti, Sarah Mounedji and Douglas Vernimmen
Differentiation of multipotent cells into highly specialised lineages requires key tissue-specific transcription factors. In these multipotent cells, developmentally regulated genes are epigenetically primed by both active (H3K4me3) and repressive (H3K27me3) marks and these are resolved during differentiation. Our aim is to address the functionality of bivalent domains by manipulating the active/repressive epigenetic balance using specific enzymes, without the input of transcription factors. We are currently engineering fusions between transcription activator-like effector (TALE) repeat arrays and histone demethylases (full length or catalytic domain) to target specific loci, without affecting other regions in the genome.