Histone deacetylase 9 regulates choline acetyltransferase gene expression in NG108‐15 cells

Abstract

Histone deacetylases (HDACs) catalyze the removal of acetyl groups from N‐terminal lysine residues of histone tails, resulting in chromatin condensation and transcriptional repression. We have previously shown that the inhibition of HDAC activity by a general and specific inhibitor of HDACs, trichostatin A, markedly increased the gene expression of choline acetyltransferase (ChAT), the synthetic enzyme for neurotransmitter acetylcholine and a specific marker for cholinergic phenotype, in NG108‐15 cells as a model of cholinergic neurons. In the present study, we examined which HDACs are involved in the regulation of ChAT gene. In experiments using class‐specific HDAC inhibitors, class IIa HDACs were a strong candidate for involvement in the regulation of ChAT gene in NG108‐15 cells. In addition, the expression of HDAC9, a class IIa enzyme, was dramatically decreased at the level of mRNA and protein during dibutyryl cyclic‐AMP‐induced cholinergic differentiation, whereas class I and other class IIa HDACs were not. Furthermore, the knockdown of HDAC9 by siRNA induced ChAT gene expression in proliferating cells. These results suggest that HDAC9 plays a key regulatory role in the acquisition of cholinergic phenotypes in NG108‐15 cells. This study was supported, in part, by a Research Fellowship of the Japan Society for the Promotion of Science to SA.