Genome-wide binding map of the histone deacetylase Rpd3 in yeast

We describe the genome-wide distribution of the histone deacetylase and repressor Rpd3 and its associated proteins Ume1 and Ume6 in Saccharomyces cerevisiae. Using a new cross-linking protocol, we found that Rpd3 binds upstream of many individual genes and upstream of members of gene classes with similar functions in anabolic processes. In addition, Rpd3 is preferentially associated with promoters that direct high transcriptional activity. We also found that Rpd3 was absent from large sub-telomeric domains. We show by co-immunoprecipitation and by the high similarity of their binding maps that Ume1 interacts with Rpd3. In contrast, despite the known role of Ume6 in Rpd3 recruitment, only a limited number of the genes targeted by Rpd3 are also enriched for (or targeted by) Ume6. This suggests that Rpd3 is brought to many promoters by alternative recruiters, some of which may bind the putative cis-regulatory DNA elements that we have identified in sets of Rpd3 target genes. Finally, we show that comparing the genome-wide pattern of Rpd3 binding with gene expression and histone acetylation in the rpd3 Delta mutant strain reveals new sites of Rpd3 function.