Activation of MHC class I, II, and CD40 gene expression by histone deacetylase inhibitors

Epigenetic mechanisms are involved in regulating chromatin structure and ge ne expression through repression. In this study, we show that histone deace tylase inhibitors (DAIs) that alter the acetylation of histones in chromati n enhance the expression of several genes on tumor cells including: MHC cla ss I, II, and the costimulatory molecule CD40, Enhanced transcription resul ts in a significant increase In protein expression on the tumor cell surfac e, and expression can be elicited on some tumors that are unresponsive to I FN-gamma, The magnitude of induction of these genes cannot be explained by the effect of DAIs on the cell cycle or enhanced apoptosis. Induction of cl ass II genes by DAIs was accompanied by activation of a repressed class II transactivator gene in a plasma cell tumor but, in several other tumor cell lines, class II was induced in the apparent absence of class II transactiv ator transcripts. These findings also suggest that the abnormalities observ ed in some tumors in the expression of genes critical to tumor immunity may result from epigenetic alterations in chromatin and gene regulation in add ition to well-established mutational mechanisms.