Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cells, Cultured / enzymology
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DNA-Binding Proteins / genetics*
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Gene Expression Regulation, Enzymologic / physiology
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Histone Deacetylases / genetics*
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Histone Deacetylases / metabolism*
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism
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Protein Binding / physiology
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Protein Structure, Tertiary
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Rabbits
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Saccharomyces cerevisiae Proteins*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / physiology
Substances
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DNA-Binding Proteins
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Multienzyme Complexes
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Repressor Proteins
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SIN3 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Histone Deacetylases