Histone deacetylases (HDACs) catalyze the deacetylation of core histones, resulting in tightening of nucleosomal integrity, restriction of the access of transcription factors, and suppression of transcription. HDACs also play an important role in mediating nuclear receptor functions by forming co-repressor complexes with nuclear receptors in the absence of ligands. They are also involved in mediating other transcription regulatory pathways by associating with transcription factors, such as E2F, TFIIE, TFIIF, NF-κB, p300, Stat3, p53, and the retinoblastoma (Rb) protein. HDAC8 is a Class I HDAC which is related to the yeast HDAC Rpd3. It is primarily localized to the nucleus with ubiquitous distribution throughout human cell lines and tissues. By modifying chromatin structure and other non-histone proteins, HDACs play important roles in controlling complex biological events, including cell development, differentiation, programmed cell death, angiogenesis, and inflammation. Considering these major roles, it is conceivable that dysregulation of HDACs and subsequent imbalance of acetylation and deacetylation may be involved in the pathogenesis of various diseases, including cancer and inflammatory diseases.
