Fig. 1. Mechanisms for the inhibition of gene transcription by histone deacetylase 9 (HDAC9). HDAC9 inhibits gene transcription by inducing deacetylation of transcription factors (TFs) or in the promoter region of genes. (1) HDAC9 directly binds to C-terminal-binding protein (CtBP) and HDAC3, which are recruited to a TF to assemble a co-repressor complex. Then, the co-repressor complex deacetylates histones in the promoter region of a gene, thereby suppressing gene transcription. (2) HDAC9 binds to a TF for its deacetylation, which inhibits the transcriptional activity. (3) Kinases, such as minibrain-related kinase and calcium calmodulin-dependent protein kinase, phosphorylate the nuclear localization signal region of HDAC9 for subsequent 14-3-3 binding, which leads to the exit of HDAC9 from the nucleus and therefore a loss of its activity.