Abstract
Neuropeptides serve as neurohormones and local paracrine regulators that control neural networks regulating behavior, endocrine system and sensorimotor functions. Their expression is characterized by exceptionally restricted profiles. Circuit-specific and adaptive expression of neuropeptide genes may be defined by transcriptional and epigenetic mechanisms controlled by cell type and subtype sequence-specific transcription factors, insulators and silencers. The opioid peptide dynorphins play a critical role in neurological and psychiatric disorders, pain processing and stress, while their mutations cause profound neurodegeneration in the human brain. In this review, we focus on the prodynorphin gene as a model for the in-depth epigenetic and transcriptional analysis of expression of the neuropeptide genes. Prodynorphin studies may provide a framework for analysis of mechanisms relevant for regulation of neuropeptide genes in normal and pathological human brain.
Highlights
Neuropeptides serve as neurohormones and local paracrine regulators
Transcription of the human PDYN gene is highly plastic resulting in generation of a variety of mRNAs that give rise to several proteins serving as opioid peptide precursors, or nuclear proteins that may regulate transcriptional and epigenetic processes
The opioid peptide sequences in the PDYN gene overlap with or are situated in close proximity to multiple TSSs, splice junctions, and CpG-SNP that is associated with psychiatric phenotype (Figure 6b)
Summary
Neuropeptides serve as neurohormones and local paracrine regulators. They control activity of neural circuits processing information relevant for behavioral, sensorimotor, endocrine and other processes [1]. Electron microscopic analysis of rat nucleus accumbens demonstrated the presence of Pdyn protein and dynorphin A in the neuronal nuclei along with its location in the smooth endoplasmic reticulum [47] Proenkephalin, another opioid peptide precursor, was found in the cell nucleus in several cell lines [48,49]. Bioinformatics analysis of PDYN, proenkephalin and proopiomelanocortin predicts that these opioid peptide precursors may serve as DNA-binding proteins They have zinc-finger and helix-loop-helix domains that are similar to those of twist, hunchback, tal and lil-1 transcription factors [50]. Transcription of the human PDYN gene is highly plastic resulting in generation of a variety of mRNAs that give rise to several proteins serving as opioid peptide precursors, or nuclear proteins that may regulate transcriptional and epigenetic processes
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