HDA1 AND RPD3 ARE MEMBERS OF DISTINCT YEAST HISTONE DEACETYLASE COMPLEXES THAT REGULATE SILENCING AND TRANSCRIPTION

Increased histone acetylation has been correlated with increased trans cription, and regions of heterochromatin are generally hypoacetylated. In investigating the cause-and-effect relationship between histone ac etylation and gene activity, we have characterized two yeast histone d eacetylase complexes. Histone deacetylase-A (HDA) is an approximate to 350-kDa complex that is highly sensitive to the deacetylase inhibitor trichostatin A. Histone deacetylase-B (HDB) is an approximate to 600- kDa complex that is much less sensitive to trichostatin A. The HDA1 pr otein (a subunit of the HDA activity) shares sequence similarity to RP D3, a factor required for optimal transcription of certain yeast genes . RPD3 is associated with the HDB activity. HDA1 also shares similarit y to three new open reading frames in yeast, designated HOS1, HOS2, an d HOS3. We find that both hda1 and rpd3 deletions increase acetylation levels in vivo at all sites examined in both core histones H3 and H4, with rpd3 deletions having a greater impact on histone H4 lysine posi tions 5 and 12. Surprisingly, both hda1 and rpd3 deletions increase re pression at telomeric loci, which resemble heterochromatin with rpd3 h aving a greater effect. In addition, rpd3 deletions retard full induct ion of the PHO5 promoter fused to the reporter lacZ. These data demons trate that histone acetylation state has a role in regulating both het erochromatic silencing and regulated gene expression.