Histone deacetylase 9 as a negative regulator for choline acetyltransferase gene in NG108-15 neuronal cells

The biological function of histone deacetylases (HDACs), namely, repression of gene expression by removing an acetyl group from a histone N-terminal tail, plays an important role in numerous biological processes such as cell cycle, differentiation, and apoptosis in the development of individual tissues, including the brain. We previously showed the possible role of HDAC activity in the regulation of gene expression of choline acetyltransferase (ChAT), a specific marker for cholinergic neurons and their function, in NG108-15 neuronal cells as an in vitro model of cholinergic neurons. The objectives of the present study were to specify key HDACs and investigate the essential role of HDACs in ChAT gene regulation in NG108-15 cells. The experiments using different types of HDAC inhibitors indicated that class IIa HDACs substantially participate in the regulation of ChAT gene expression. In addition, HDAC9, a class IIa enzyme, was dramatically decreased at the protein levels, and dissociated from the promoter region of ChAT gene during neuronal differentiation. Furthermore, knockdown of HDAC9 by siRNA increased ChAT gene expression in undifferentiated cells. These findings demonstrate that HDAC9 is responsible for repressing ChAT gene expression in NG108-15 neuronal cells, and thus plays an important role in cholinergic differentiation.

▶The selective inhibitor for class IIa HDACs increased ChAT gene expression. ▶HDAC9 protein was decreased during neuronal differentiation. ▶The occupancy by HDAC9 at ChAT gene promoter was lowered after differentiation. ▶RNAi for HDAC9 increased ChAT gene expression. ▶HDAC9 is a negative regulator for ChAT gene expression.