Adenovirus E1A TRRAP-targeting domain-mediated enhancement of MYC association with the NuA4 complex activates a panel of MYC target genes enriched for gene expression and ribosome biogenesis.
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ABSTRACT: Cellular transformation by adenovirus E1A requires targeting TRRAP, a scaffold protein which helps assemble histone acetyltransferase complexes, including the NuA4 complex. We recently reported that E1A and E1A 1-80 (N-terminal 80 aa) promote association of the proto-oncogene product MYC with the NuA4 complex. The E1A N-terminal TRRAP-targeting (ET) domain is required for E1A 1-80 to interact with the NuA4 complex. We demonstrate that an ET-MYC fusion associates with the NuA4 complex more efficiently than does MYC alone. Because MYC regulates genes for multiple cellular pathways, we performed global RNA-sequence analysis of cells expressing MYC or ET-MYC, and identified a panel of genes (262) preferentially activated by ET-MYC and significantly enriched in genes involved in gene expression and ribosome biogenesis, suggesting that E1A enhances MYC association with the NuA4 complex to activate a set of MYC target genes likely involved in cellular proliferation and cellular transformation by E1A and by MYC.
SUBMITTER: Zhao LJ
PROVIDER: S-EPMC5790114 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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