THE HISTONE DEACETYLASE RPD3 COUNTERACTS GENOMIC SILENCING IN DROSOPHILA AND YEAST

BOTH position-effect variegation (PEV)(1,2) in Drosophila and telomeri c position-effect in yeast (TPE)(3-5) result from the mosaic inactivat ion of genes relocated next to a block of centromeric heterochromatin or next to telomeres. In many aspects, these phenomena are analogous t o other epigenetic silencing mechanisms, such as the control of homeot ic gene clusters(6), X-chromosome inactivation(7) and imprinting in ma mmals(8), and mating-type control in yeast(5), Dominant mutations that suppress or enhance PEV are thought to encode either chromatin protei ns or factors that directly affect chromatin structure(1), We have ide ntified an insertional mutation in Drosophila that enhances PEV and re duces transcription of the gene in the eye-antenna imaginal disc, The gene corresponds to that encoding the transcriptional regulator RPD3 i n yeast(9,10), and to a human histone deacetylase(11). In yeast, RRD3- deletion strains show enhanced TPE, suggesting a conserved role of the histone deacetylase RPD3 in counteracting genomic silencing, This fun ction of RPD3, which is in contrast to the general correlation between histone acetylation and increased transcription, might be due to a sp ecialized chromatin structure at silenced loci.