Abstract
Histone acetyltransferases (HAT) play a critical role in transcriptional control by relieving repressive effects of chromatin, and yet how HATs themselves are regulated remains largely unknown. Here, it is shown that Twist directly binds two independent HAT domains of acetyltransferases, p300 and p300/CBP-associated factor (PCAF), and directly regulates their HAT activities. The N terminus of Twist is a primary domain interacting with both acetyltransferases, and the same domain is required for inhibition of p300-dependent transcription by Twist. Adenovirus E1A protein mimics the effects of Twist by inhibiting the HAT activities of p300 and PCAF. These findings establish a cogent argument for considering the HAT domains as a direct target for acetyltransferase regulation by both a cellular transcription factor and a viral oncoprotein.
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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Acetyltransferases / antagonists & inhibitors
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Acetyltransferases / metabolism*
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Acetyltransferases / physiology
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Adenovirus E1A Proteins / metabolism
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Adenovirus E1A Proteins / physiology*
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Animals
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COS Cells
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Cells, Cultured
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E1A-Associated p300 Protein
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Enzyme Activation
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Histone Acetyltransferases
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Mice
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Nuclear Proteins / physiology
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Oncogene Proteins, Viral / metabolism
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Oncogene Proteins, Viral / physiology
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Peptide Fragments / metabolism
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Peptide Fragments / physiology
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Saccharomyces cerevisiae Proteins*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Trans-Activators / physiology
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcription, Genetic
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Twist-Related Protein 1
Substances
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Adenovirus E1A Proteins
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Nuclear Proteins
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Oncogene Proteins, Viral
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Peptide Fragments
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Saccharomyces cerevisiae Proteins
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TWIST1 protein, human
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Trans-Activators
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Transcription Factors
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Twist-Related Protein 1
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Acetyltransferases
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E1A-Associated p300 Protein
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Ep300 protein, mouse
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Histone Acetyltransferases