Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene.[5][6][7]
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation / deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.[7]
Histone deacetylase 8 is involved in skull morphogenesis[8] and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex.[9]
HDAC8 has been linked to number of disease states notably to acute myeloid leukemia and is related to actin cytoskeleton in smooth muscle cells. siRNA targeting HDAC8 showed anticancer effects.[10] Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas.[11] In addition the HDAC8 enzyme has been implicated in the pathogenesis of neuroblastoma.[12] Therefore, there has been interest in developing HDAC8 selective inhibitors.[13][14] At least 20 disease-causing mutations in this gene have been discovered.[15]