Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo

David Kadosh, Kevin Struhl

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

Eukaryotic organisms from yeast to human contain a multiprotein complex that includes Rpd3 histone deacetylase and Sin3 corepressor. The Sin3-Rpd3 complex, when recruited to promoters by specific DNA-binding proteins, can direct transcriptional repression of specific classes of target genes. It has been proposed that the histone deacetylase activity of Rpd3 is important for repression, but direct evidence is lacking. Here, we describe four Rpd3 derivatives with mutations in evolutionarily invariant histidine residues in a putative deacetylation motif. These Rpd3 mutants lack detectable histone deacetylase activity in vitro, but interact normally with Sin3 in vivo. In yeast cells, these catalytically inactive mutants are defective for transcriptional repression. They retain some residual Rpd3 function in vivo, however, suggesting that repression by the Sin3-Rpd3 complex may not be attributable exclusively to its intrinsic histone deacetylase activity. Finally, we show that a human Rpd3 homolog can interact with yeast Sin3 and repress transcription when artificially recruited to a promoter. These results suggest that the histone deacetylase activity of Rpd3 is important, but perhaps not absolutely required, for transcriptional repression in vivo.

Original languageEnglish (US)
Pages (from-to)797-805
Number of pages9
JournalGenes and Development
Volume12
Issue number6
StatePublished - Mar 15 1998
Externally publishedYes

Fingerprint

Histone Deacetylases
Yeasts
Multiprotein Complexes
Co-Repressor Proteins
DNA-Binding Proteins
Histidine
Mutation
Genes

Keywords

  • Chromatin
  • Gene regulation
  • Histone deacetylation
  • Transcriptional repression

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo. / Kadosh, David; Struhl, Kevin.

In: Genes and Development, Vol. 12, No. 6, 15.03.1998, p. 797-805.

Research output: Contribution to journalArticle

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