Role of Pleiohomeotic in Targeted Gene Silencing by Polycomb Group Proteins

Epigenetic regulation refers to effects on eukaryotic gene expression that are inherited through cell divisions. Research over the last decade has established a critical role for covalent chromatin modifications in the perpetuation of gene expression patterns. However, how specialized DNA sequence elements can bring a linked gene under epigenetic control has remained unclear. Drosophila Polycomb response elements (PREs) are cis-acting epigenetic DNA elements that maintain segment-specific silencing of linked enhancers in a PcG gene-dependent manner and function as chromosomal tethers for Polycomb group proteins (PcG) proteins. The mechanism by which they are targeted to PREs remains largely unclear. One of the major classes of PcG repressor complexes (PRCs) is PRC1. PRC1-type complexes harbor the core subunits Posterior sex combs (PSC), Polyhomeotic (PH), Polycomb (PC) and dRING1, and several other proteins. Because PREs function in transgenes, there is possibly a DNA sequence code that can impose PcG control. However, the nature of this PRE code is still elusive. Recent studies have shed more light in this area. Sequence-specific DNA-binding proteins have been implicated in recruiting PcG complexes to PREs. One of the key players is the Drosophila homologue of the mammalian transcription factor Yin Yang 1 (YY1), which is the DNA-binding protein Pleiohomeotic (PHO). PHO binding elements are essential in PcG silencing in vivo and PHO mutants result in PcG phenotypes in flies. In this thesis, we report on the role of PHO in targeted gene silencing by PcG proteins.