Ethanol alters neural activity through interaction with multiple
neurotransmitters and
neuromodulators. The endogenous
opioid system seems to play a key role, since the
opioid receptor antagonist naltrexone (ReVia®) attenuates craving for alcohol. We recently reported that
ethanol and
acetaldehyde, the first product of
ethanol metabolism, affect transcription of
opioid system genes in human SH-SY5Y
neuroblastoma cells. In the current study, potential epigenetic mechanisms were investigated to clarify these effects on
prodynorphin gene expression. DNA methylation was analyzed by
bisulfite pyrosequencing, and
chromatin immunoprecipitation was used to assess putative specific histone modifications at the
prodynorphin gene promoter. The results demonstrated a temporal relationship between selective
chromatin modifications induced by
ethanol and
acetaldehyde and changes in
prodynorphin gene expression quantitated by real-time qPCR. DNA methylation was not altered in any of the experimental conditions used. The epigenetic changes may precede gene transcription, and histone modifications might keep the
prodynorphin gene in a poised state for later reactivation. A link has been observed between gene expression alterations and selective epigenetic modulation in the
prodynorphin promoter region, demonstrating a specificity of the changes induced by
ethanol and
acetaldehyde. The latter may be mediating
ethanol effects at the genomic level.