General transcription factors bind promoters repressed by Polycomb group proteins

To maintain cell identity during development and differentiation, mechanism s of cellular memory have evolved that preserve transcription patterns in a n epigenetic manner. The proteins of the Polycomb group (PcG) are part of s uch a mechanism, maintaining gene silencing. They act as repressive multipr otein complexes that may render target genes inaccessible to the transcript ional machinery(1,2), inhibit chromatin remodelling(3,4), influence chromos ome domain topology(5) and recruit histone deacetylases (HDACs)(6). PcG pro teins have also been found to bind to core promoter regions(7), but the mec hanism by which they regulate transcription remains unknown. To address thi s, we used formaldehyde-crosslinked chromatin immunoprecipitation (X-ChIP) to map TATA-binding protein (TBP), transcription initiation factor IIB (TFI IB) and IIF (TFIIF), and dHDAC1 (RPD3) across several Drosophila promoter r egions. Here we show that binding of PcG proteins to repressed promoters do es not exclude general transcription factors (GTFs) and that depletion of P cG proteins by double-stranded RNA interference leads to de-repression of d evelopmentally regulated genes. We further show that PcG proteins interact in vitro with GTFs. We suggest that PcG complexes maintain silencing by inh ibiting GTF-mediated activation of transcription.