TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity in yeast

TUP1 is recruited to and represses genes that regulate mating, glucose and oxygen use, stress response, and DNA damage. It is shown here that disrupti on of either TUP1 or histone deacetylase HDA1 causes histone H3/H2B-specifi c hyperacetylation next to the TUP1 binding site at the stress-responsive E NA1 promoter. It is also shown that TUP1 interacts with HDA1 in vitro. Thes e data indicate that TUP1 mediates localized histone deacetylation through HDA1. Interestingly, RPD3 deacetylates the ENA1 coding region, and both dea cetylases contribute to ENA1 repression. However, epistasis analysis argues that only HDA1 and TUP1 are likely to function in the same pathway. These data define gene and histone targets of HDA1 and illustrate the role of his tone deacetylation in TUP1 repression.