Tissue-specific DNA methylation of the human prodynorphin gene in post-mortem brain tissues and PBMCs

Pharmacogenet Genomics. 2011 Apr;21(4):185-96. doi: 10.1097/FPC.0b013e32833eecbc.


Objective: Dynorphins, the endogenous ligands for the κ opioid receptor, are implicated in neuropsychiatric disorders through modulation of basal and stimuli-induced dopaminergic, glutamatergic, and serotonergic tones. Expression of the prodynorphin gene (PDYN) is critical for rewarding properties of drugs of abuse and stress-induced responses. Epigenetic factors, such as DNA methylation, play an important role in modulation of gene expression.

Methods: We analyzed DNA methylation patterns of three CpG-rich regions of PDYN, a CpG island, and cluster A in the proximal promoter, and cluster B in coding exon 4, by bisulfite sequencing of DNA from the caudate and anterior cingulate cortex from post-mortem brain of 35 individuals (22 HIV seropositive), and in peripheral blood mononuclear cells from 21 of these individuals.

Results: We found remarkably similar patterns of methylation across CpG sites in these tissues. However, there were tissue-specific differences in methylation levels (P=0.000001) of the CpG island: higher levels in peripheral blood mononuclear cells (82%) than in the brain tissues, the caudate (62%), and the anterior cingulate cortex (44%). But there was higher PDYN expression in the caudate than in the anterior cingulate cortex. In contrast, cluster A near the transcription start site is hypomethylated.

Conclusion: This DNA methylation profile of the PDYN gene is typical for primary responsive genes with regulatory elements for both basal and tissue-specific transcription. Our findings provide a rationale for further studies of the role of other epigenetic factors in the regulation of PDYN expression in individuals with psychiatric and neurological disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain / metabolism*
  • CpG Islands
  • DNA Methylation*
  • Enkephalins / genetics*
  • Epigenomics
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Protein Precursors / genetics*
  • RNA, Messenger / metabolism


  • Enkephalins
  • Protein Precursors
  • RNA, Messenger
  • preproenkephalin