ABSTRACT
The transcriptional capacity of genes is intricately controlled in part by the opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), which contribute to the structural remodeling of chromatin by adding or removing, respectively, acetyl groups from the amino-terminal lysine residues of histones. Acetylation is one of the many posttranslational histone modifications and promotes transcription by locally expanding chromatin to permit the access of regulatory proteins to DNA, whereas removal of acetyl groups leads to transcriptional repression via chromatin condensation. These modifications of histones by acetylation are among the epigenetic mechanisms controlling gene expression that is suggested to contribute to malignant transformation [1-4]. HDACs have been implicated in the actions of well-known cellular oncogenes and tumor suppressor genes [5-8], and a tumor suppressor role for HATs has been described [9,10]. Moreover, associations have been reported between the expression levels of HDAC enzymes and various features of human malignancies, such as steroid hormone receptor status and clinical outcome in breast cancer [11-13], prognosis in lung cancer [14], and response to therapy in acute myeloblastic leukemia [15]. Collectively, these studies suggest a role for histone acetylation in the development and progression of cancer.
