Down-regulation of transcription of the MHC class I genes in HPV16 tumorigenic cells is partly due to HPV16E7 associated with the MHC class I promoter and repressed chromatin activation. In this study, we further demonstrated that HPV16E7 is physically associated with a putative RXR beta binding motif (GGTCA) of the proximal promoter of the MHC class I genes by using reporter transcriptional assays and chromatin immunoprecipitation assays. Our data also provide evidence that HPV16E7 inhibits TNF alpha-induced up-regulation of MHC class I transcription by impaired nuclear translocation of NF-kappa B. More importantly, CaSki tumor cells treated with TSA and transfected with the constitutively active mutant form of IKK-alpha (which can activate NF-kappa B directly) showed a maximal level of up-regulation of MHC-I expression. Taken together, our results suggest that HPV16E7 may employ two independent mechanisms to ensure that either the constitutive or inducible transcription of MHC class I genes is down-regulated. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.