Gene Silencing and Chromatin Modification by Polycomb Complexes in Flies and Humans

This chapter deals with gene slicing and chromatic modification by polycomb complexes. Polycomb group (PcG) proteins are general chromatin repressors that are conserved from flies to humans. Most PcG members were identified through genetic screens in Drosophila on the basis of their roles in silencing homeotic (Hox) genes. In the most severe PcG mutants, the ABD-B Hox protein accumulates throughout the A–P axis, which transforms most segments into copies of the eighth abdominal segment. Thus, complete loss of PcG silencing in fly embryos causes wholesale disruption of segmental differentiation. Under conditions of less severe PcG loss, adult flies display modest alterations in segment identity yielding, for example, legs with extra sex comb bristles. Genetic studies show that individual subunits of these PcG complexes are each required for Hox gene silencing in vivo, indicating that these biochemically separable complexes work together to achieve silent chromatin states. This chapter further discusses the molecular functions and workings of each PcG complex. Following this, it describes the functions of the three PcG complexes. It also deals with PcG partnership with other chromatin silencing enzymes and looks into polycomb silencing in stem cell maintenance. Finally, it describes the connection between PcG repressors and cancer.