Abstract
Acetylation of histones by p300/CBP and PCAF is considered to be a critical step in transcriptional regulation. In order to understand the role of cellular activities that modulate histone acetylation and transcription, we have purified and characterized a multiprotein cellular complex that potently inhibits the histone acetyltransferase activity of p300/CBP and PCAF. We have mapped a novel acetyltransferase-inhibitory domain of this INHAT (inhibitor of acetyltransferases) complex that binds to histones and masks them from being acetyltransferase substrates. Endogenous INHAT subunits, which include the Set/TAF-Ibeta oncoprotein, associate with chromatin in vivo and can block coactivatormediated transcription when transfected in cells. We propose that histone masking by INHAT plays a regulatory role in chromatin modification and serves as a novel mechanism of transcriptional regulation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Acetyltransferases / chemistry
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Acetyltransferases / genetics
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Acetyltransferases / metabolism*
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Chromatin / genetics
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Chromatin / metabolism
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Chromosomal Proteins, Non-Histone / genetics*
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Chromosomal Proteins, Non-Histone / metabolism*
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Chromosome Mapping
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DNA-Binding Proteins
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HeLa Cells
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Histone Acetyltransferases
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Histone Chaperones
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Histones / genetics*
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Histones / metabolism*
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Humans
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Protein Binding / genetics
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Protein Structure, Tertiary
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Proteins / genetics
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Proteins / metabolism
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Receptors, Retinoic Acid / physiology
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Saccharomyces cerevisiae Proteins*
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Signal Transduction / physiology
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Transcription Factors*
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Transcription, Genetic / physiology
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p300-CBP Transcription Factors
Substances
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Cell Cycle Proteins
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Chromatin
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Histone Chaperones
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Histones
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Nuclear Proteins
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Phosphoproteins
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Proteins
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Receptors, Retinoic Acid
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SET protein, human
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor