E1A12S-mediated activation of the adenovirus type 12 E2 promoter depends on the histone acetyltransferase activity of p300/CBP.
Activation of the transcription unit early region 2 (E2) promoter of the oncogenic adenovirus serotype 12 (Ad12), which regulates the expression of proteins essential for viral replication, requires the assembly of a ternary complex consisting of cAMP response element-binding protein (CREB)-1/activating transcription factor (ATF)-1, the Ad12 12S oncogene product of early region 1A (E1A(12S)), and the co-activator p300/CBP on the E2(Ad12) cAMP response element (E2-CRE). Here we show that the active E2(Ad12) promoter is associated with acetylated histone H4 whereas an E2-CRE point-mutated promoter which is transcriptionally inactive due to its inability to assemble this ternary complex is not bound by acetylated histone H4. The histone deacetylase 1 as well as Roscovitine, which blocks the activation of the histone acetyltransferase (HAT) activity of CBP by cyclin E-Cdk2, prevents E2(Ad12) promoter activation through E1A(12S). p300/CBP counteracts the repressive function of histone deacetylase 1 in a HAT domain-dependent manner whereas the p300/CBP-associated factor PCAF failed to rescue E2(Ad12) promoter activity. E1A(12S) bound p300/CBP displays strong HAT activity. Most interestingly, E1A(12S)-mediated activation of the E2(Ad12) promoter correlates well with the ability of the viral protein to associate with the HAT activity of p300/CBP in vivo. Taken together these data indicate that the recruitment of the HAT activity of p300/CBP by E1A(12S) plays an important role in E2(Ad12) promoter activation.
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Institute of Molecular Biology (Cancer Research), University of Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany.
Lehmkuhler
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Kuhn
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Esche
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Brockmann
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D000123:Acetyltransferases / Q000378:metabolism*; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology*; D017502:Adenovirus E2 Proteins / Q000235:genetics*; D000818:Animals; D050882:CREB-Binding Protein; D002460:Cell Line; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D017502:Adenovirus E2 Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases