The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex.
Binding of the C-terminal binding protein, CtBP, to the adenovirus E1A moiety of a Gal4-E1A fusion protein abolishes conserved region (CR) 1-dependent transcription activation. In contrast, a non-promoter targeted E1A peptide, capable of binding CtBP, can induce transcription from the proliferating cell nuclear antigen (PCNA) promoter. CtBP is shown here to bind the histone deacetylase HDAC1, suggesting that a promoter targeted CtBP-HDAC1 complex can silence transcription from the PCNA promoter through a deacetylation mechanism. Expression of the CtBP binding domain of E1A is sufficient to alleviate repression, possibly due to the displacement of the CtBP-HDAC1 complex from the promoter.
Sundqvist
A
A
Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Sweden.
Sollerbrant
K
K
Svensson
C
C
D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000429:Alcohol Oxidoreductases; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases