Abstract
Mammalian rRNA genes are preceded by a terminator element that is recognized by the transcription termination factor TTF-I. In exploring the functional significance of the promoter-proximal terminator, we found that TTF-I associates with the p300/CBP-associated factor PCAF, suggesting that TTF-I may target histone acetyltransferase to the rDNA promoter. We demonstrate that PCAF acetylates TAF(I)68, the second largest subunit of the TATA box-binding protein (TBP)-containing factor TIF-IB/SL1, and acetylation enhances binding of TAF(I)68 to the rDNA promoter. Moreover, PCAF stimulates RNA polymerase I (Pol I) transcription in a reconstituted in vitro system. Consistent with acetylation of TIF-IB/SL1 being required for rDNA transcription, the NAD(+)-dependent histone deacetylase mSir2a deacetylates TAF(I)68 and represses Pol I transcription. The results demonstrate that acetylation of the basal Pol I transcription machinery has functional consequences and suggest that reversible acetylation of TIF-IB/SL1 may be an effective means to regulate rDNA transcription in response to external signals.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Acetyltransferases / antagonists & inhibitors
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Acetyltransferases / metabolism*
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Animals
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DNA, Ribosomal
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation, Enzymologic
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Gene Silencing
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Histone Acetyltransferases
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Histone Deacetylases / metabolism
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Hydroxamic Acids / pharmacology
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Mice
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Pol1 Transcription Initiation Complex Proteins*
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Protein Binding
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Protein Subunits
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RNA Polymerase I / biosynthesis*
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RNA Polymerase I / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
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Silent Information Regulator Proteins, Saccharomyces cerevisiae*
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Sirtuin 2
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Sirtuins
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TATA-Box Binding Protein
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Terminator Regions, Genetic
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Trans-Activators / metabolism
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Transcription Factors / metabolism*
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Transcription, Genetic
Substances
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DNA, Ribosomal
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DNA-Binding Proteins
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Hydroxamic Acids
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Pol1 Transcription Initiation Complex Proteins
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Protein Subunits
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Silent Information Regulator Proteins, Saccharomyces cerevisiae
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TAF(i)68 protein, mouse
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TATA-Box Binding Protein
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Trans-Activators
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Transcription Factors
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transcription initiation factor TIF-IB
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trichostatin A
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Acetyltransferases
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Histone Acetyltransferases
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RNA Polymerase I
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SIR2 protein, S cerevisiae
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Sirtuin 2
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Sirtuins
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Histone Deacetylases