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/activa...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-12, Vol.275 (51), p.40554-40560
Main Authors: Fax, Peter, Lehmkühler, Oliver, Kühn, Claudine, Esche, Helmut, Brockmann, Dieter
Format: Article
Language:English
Subjects:
Acetyltransferases - metabolism
Adenovirus E1A Proteins - genetics
Adenovirus E1A Proteins - physiology
Adenovirus E2 Proteins - genetics
Animals
Cell Line
CREB-Binding Protein
Histone Acetyltransferases
Humans
Nuclear Proteins - metabolism
Promoter Regions, Genetic
Saccharomyces cerevisiae Proteins
Trans-Activators - metabolism
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Summary: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 (E1A12S), and the co-activator p300/CBP on the E2Ad12 cAMP response element (E2-CRE). Here we show that the active E2Ad12 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 E2Ad12 promoter activation through E1A12S. 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 E2Ad12 promoter activity. E1A12S bound p300/CBP displays strong HAT activity. Most interestingly, E1A12S-mediated activation of the E2Ad12promoter 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 E1A12S plays an important role in E2Ad12 promoter activation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M004626200