Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription.
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.
Muth
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Division of Molecular Biology of the Cell II, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Nadaud
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Grummt
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Voit
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D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D035463:Pol1 Transcription Initiation Complex Proteins; D011485:Protein Binding; D021122:Protein Subunits; D012318:RNA Polymerase I / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D035181:TATA-Box Binding Protein; D013728:Terminator Regions, Genetic; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; D035463:Pol1 Transcription Initiation Complex Proteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C423702:TAF(i)68 protein, mouse; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors; C063660:transcription initiation factor TIF-IB; C012589:trichostatin A; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D012318:RNA Polymerase I; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases