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Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain.
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2017 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, p. 1-14Article in journal (Refereed) Epub ahead of print
Abstract [en]

Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF). USF2 activates PDYN transcription in model systems, and binds to nonmethylated CGI in dlPFC. USF2 and PDYN expression is correlated, and USF2 and PDYN proteins are co-localized in dlPFC. Segregation of activatory TF and repressive CGI methylation may ensure contrasting PDYN expression in neurons and glia in human brain.

Place, publisher, year, edition, pages
2017. p. 1-14
Keywords [en]
DNA methylation, cell type-specific expression, human brain, neuropeptides, transcription
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-343193DOI: 10.1093/cercor/bhx181PubMedID: 28968778OAI: oai:DiVA.org:uu-343193DiVA, id: diva2:1185688
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-26

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