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

• Published in: Genetics (Austin) 1998-02, Vol.148 (2), p.657-667
• Main Authors: DeSilva, H. (Cornell University Graduate School of Medical Sciences, New York, NY.), Lee, K, Osley, M.A
• Format: Article
• Language: English
• Subjects: ADN RECOMBINADO; ADN RECOMBINE; AMINO ACID SEQUENCES; ARN MENSAJERO; ARN MESSAGER; BETA GALACTOSIDASA; BETA GALACTOSIDASE; BINDING PROTEINS; BINDING SITES; CHEMICAL COMPOSITION; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; DELETIONS; DNA Mutational Analysis; EXPRESION GENICA; EXPRESSION DES GENES; FACTEUR DE TRANSCRIPTION; FACTORES DE TRANSCRIPCION; Fungal Proteins - genetics; Fungal Proteins - metabolism; GENE; GENE EXPRESSION; Gene Expression Regulation, Fungal - genetics; GENE OVEREXPRESSION; GENES; Genetics; HISTONAS; HISTONE; HISTONES; Histones - genetics; HTA1 PROMOTER; INTERACTIONS; MESSENGER RNA; MUTACION; MUTATION; Mutation - genetics; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phenotype; Promoter Regions, Genetic - genetics; PROMOTERS; PROTEINAS AGLUTINANTES; PROTEINE DE LIAISON; RECOMBINANT DNA; REGULATORY GENES; REPORTER GENES; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - metabolism; Repressor Proteins - physiology; RNA, Messenger - metabolism; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; TRANSCRIPCION; TRANSCRIPTION; TRANSCRIPTION FACTORS; TRANSCRIPTION REPRESSORS; Transcription, Genetic - genetics; Yeast
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1093/genetics/148.2.657

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.