Epigenetic repression of p16(INK4A) by latent Epstein-Barr virus requires the interaction of EBNA3A and EBNA3C with CtBP.

ABSTRACT: As an inhibitor of cyclin-dependent kinases, p16(INK4A) is an important tumour suppressor and inducer of cellular senescence that is often inactivated during the development of cancer by promoter DNA methylation. Using newly established lymphoblastoid cell lines (LCLs) expressing a conditional EBNA3C from recombinant EBV, we demonstrate that EBNA3C inactivation initiates chromatin remodelling that resets the epigenetic status of p16(INK4A) to permit transcriptional activation: the polycomb-associated repressive H3K27me3 histone modification is substantially reduced, while the activation-related mark H3K4me3 is modestly increased. Activation of EBNA3C reverses the distribution of these epigenetic marks, represses p16(INK4A) transcription and allows proliferation. LCLs lacking EBNA3A express

SUBMITTER: Skalska L 

PROVIDER: S-EPMC2883600 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature