Drosophila Kinome and Genome-wide RNAi screens reveal novel regulators of epigenetic cell memory

Cell fate determination, a fundamental aspect of development in multicellular eukaryotes, relies on establishment of cell-type specific gene expression patterns during early development. Once established, these patterns are subsequently maintained by two groups of proteins known as Polycomb group (PcG) and Trithorax group (TrxG). Both the PcG and TrxG associate with chromatin in the form of multimeric protein complexes to maintain either a silent or an active states of gene expression, respectively. These states are epigenetically inherited through cell division and are referred to as cellular memory, a phenomenon which plays a fundamental role in cell lineage commitment and differentiation. We have successfully established a cell based reporter system in Drosophila which is sensitive to modulation of PcG and TrxG genes. We have exploited our cell based assay to perform kinome and genome-wide RNAi screens in Drosophila cells to discover novel regulators of the epigenetic cell memory. Genetic and molecular characterization of candidate genes discovered in genome-wide RNAi screen have revealed additional histone modifications like phosphorylation and acetylation which influence epigenetic cell memory. In addition to previously known H3K27 trimethylation and H2AK119ub, a combinatorial act of additional histone modifications will be discussed to maintain epigenetic cell memory.

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Dr Stefan Schoenfelder
The Cambridge Building - Kings Hedges Room