Functional dissection of yeast Hir1p, a WD repeat-containing transcriptional corepressor

The HIR1 gene product is required to repress transcription of three of the four histone gene loci in Saccharomyces cerivisiae, and like its counterpart, the HIR2 protein, it functions as a transcriptional corepressor. Although Hir1p and Hir2p are physically associated in yeast, Hir1p is able to function independently of Hir2p when it is artificially recruited to the histone HTA1 promoter. A deletion analysis of HIR1 has revealed two separate repression domains: one in its N terminus, where seven copies of the beta-transducin or WD40 motif reside, and the second in the remaining C-terminal amino acids. Overexpression of the WD repeats in a hir1delta strain complemented its Hir- phenotype, while overexpression of the C terminus in a wild-type strain caused both Hir- and Spt- phenotypes. The Hir1p C terminus physically interacted in vivo with Hir2p, and both Hir1p repression domains interacted with full-length Hir1p. It was additionally found that the Hir1p WD repeats functionally interacted with the SPT4, SPT5, and SPT6 gene products, suggesting that these repeats may direct Hir1p to different protein complexes.