Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease

► Inhibition of the HDAC3 subtype is necessary for amelioration of gene expression deficits related to HD. ► Rescue of neurodegeneration in HD flies can be achieved by treating with compounds that target class I HDACs. ► Amelioration of Htt-elicited metabolic deficits in striatal cells is correlated with potency of HDAC3 and HDAC1 inhibition. ► HDAC1 and HDAC3 accumulate in the nucleus of HD transgenic mice. ► HDAC1 and HDAC3 contribute to a repressive chromatin environment in HD.