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.
Division of Molecular Biology of the Cell II, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
V
V
Muth
S
S
Nadaud
I
I
Grummt
R
R
Voit
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