Epigenetic regulation of the human GDAP1 gene

Mutations in the ganglioside-induced differentiation-associated protein 1 (<i>GDAP1</i>) gene are linked to Charcot-Marie-Tooth (CMT) disease, a hereditary neurodegenerative condition. The protein encoded by this gene is involved in mitochondrial fission and calcium homeostasis. Recently, GDAP1 has also been implicated in the survival of patients with certain cancers. Despite its significant role in specific cellular processes and associated diseases, the mechanisms regulating <i>GDAP1</i> expression are largely unknown. Here, we show for the first time that methylation of the CpG island in the proximal promoter of the <i>GDAP1</i> gene inhibits its activity. Treating cells with low <i>GDAP1</i> expression using methyltransferase and HDAC inhibitors induced the expression of this gene and its encoded protein. This induction was associated with promoter demethylation and increased association of acetylated histones with the <i>GDAP1</i> promoter. Thus, we identified a mechanism that could be used to manipulate <i>GDAP1</i> expression.