Histone deacetylase (HDAC) inhibitors (HDIs) are documented for their role in activation and/or repression of gene expression. Currently, it is believed that HDAC inhibitors act at the histone level to alter chromatin dynamics through the inactivation of HDACs thereby resulting in historic hyperacetylation and increased transcriptional activation. However, transcriptional repression of gene expression is not explained by this model. Indeed, changes in the acetylation status of discreet lysine residues of histones associated with genes repressed by HDAC inhibitors have not been reported. Therefore, we carried out a systematic investigation of the changes in histone acetylation status at the promoter regions of two genes differentially affected by HDIs to gain a better understanding of how changes in histone acetylation correspond to changes in transcriptional activity. (C) 2008 Elsevier Inc. All rights reserved.