Polycomb Group proteins and heritable silencing of Drosophila Hox genes

Early in Drosophila embryogenesis, transcriptional repressors encoded by Ga p genes prevent the expression of particular combinations of Hox genes in e ach segment, During subsequent development, those Hox genes that were initi ally repressed in each segment remain off in all the descendent cells, even though the Gap repressors are no longer present. This phenomenon of herita ble silencing depends on proteins of the Polycomb Group (PcG) and on cis-ac ting Polycomb response elements (PREs) in the Hox gene loci, We have remove d individual PcG proteins from proliferating cells and then resupplied thes e proteins after a few or several cell generations, We show that most PcG p roteins are required throughout development: when these proteins are remove d, Hox genes become derepressed, However, we find that resupply of at least some PcG proteins can cause re-repression of Hox genes, provided that it o ccurs within a few cell generations of the loss of repression, These result s suggest a functional distinction between transcriptional repression and h eritable silencing: in at least some contexts, Hox genes can retain the cap acity to be heritably silenced, despite being transcribed and replicated, W e propose that silenced Hox genes bear a heritable, molecular mark that tar gets them for transcriptional repression. Some PcG proteins may be required to define and propagate this mark; others may function to repress the tran scription of Hox genes that bear the mark.