The exact mechanism(s) through which HDAC1 and DAXX regulate the GAD65 andGAD67 promoters are not yet fully understood. Neither the GAD67 northe GAD65 promoter has binding sequences for these factors. One possibility isthat HDAC1 and/or DAXX might employ other transcription factors to assist them in theindirect regulation of GAD expression. An example is the transcription factor Egr-1 that hasbeen found to be associated with the regulation of the GAD67 promoter (Luo et al. 2008; Zhang et al. 2010). Consistent with this, our in vitro modeldemonstrated that inhibition of either HDAC1 or DAXX expression resulted in an increasedtranscription of Egr-1 mRNA expression (Subburaju etal. 2016). A second possibility is that HDAC1 and DAXX may be a component of anenhancer complex that is operative at sites distal to the GAD67 andGAD65 promoters. Such a regulatory mechanism involving histone deactylasesactivity has been proposed for the GAD65 promoter (Pan 2012). Future studies will elucidate how HDAC1 and DAXXinfluence the GAD promoters in hippocampal GABA neurons.
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