Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression

Cell. 1997 May 2;89(3):349-56. doi: 10.1016/s0092-8674(00)80215-9.


Transcriptional repression by Mad-Max heterodimers requires interaction of Mad with the corepressors mSin3A/B. Sin3p, the S. cerevisiae homolog of mSin3, functions in the same pathway as Rpd3p, a protein related to two recently identified mammalian histone deacetylases, HDAC1 and HDAC2. Here, we demonstrate that mSin3A and HDAC1/2 are associated in vivo. HDAC2 binding requires a conserved region of mSin3A capable of mediating transcriptional repression. In addition, Mad1 forms a complex with mSin3 and HDAC2 that contains histone deacetylase activity. Trichostatin A, an inhibitor of histone deacetylases, abolishes Mad repression. We propose that Mad-Max functions by recruiting the mSin3-HDAC corepressor complex that deacetylates nucleosomal histones, producing alterations in chromatin structure that block transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured / enzymology
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Enzymologic / physiology
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism*
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Rabbits
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / physiology


  • DNA-Binding Proteins
  • Multienzyme Complexes
  • Repressor Proteins
  • SIN3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Histone Deacetylases