E1A is the component of the MHC class I enhancer complex that mediates HDAC chromatin repression in adenovirus-12 tumorigenic cells

In adenovirus-12 tumorigenic cells, the viral E1A-12 protein mediates transcriptional down-regulation of the major histocompatibility complex (MHC) class I genes by targeting the class I enhancer. Here, we demonstrate by a combination of antisense and chromatin immunoprecipitation (ChIP) analysis that E1A-12 is a physical component of the class I enhancer repression complex, known to comprise COUP-TFII and histone deacetylase 1 (HDAC1). Significantly, E1A antisense was shown to co-eliminate E1A-12 as well as HDAC1 and HDAC8, but not HDAC3, from the enhancer repression complex. Consistent with elimination of HDAC1 and HDAC8, E1A antisense also resulted in a dramatic increase in histone acetylation, a hallmark of transcriptionally active chromatin. Importantly, MHC class I antigen expression was restored on the surface of E1A antisense-transfected cells. These results demonstrate that E1A-12 is associated with the MHC class I complex and apparently mediates class I transcriptional down-regulation by enacting chromatin repression through HDAC1 and HDAC8.