uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0003-4388-1656
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-2451-4386
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-1332-7067
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Show others and affiliations
2018 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 9, p. 3129-3142Article in journal (Refereed) Published
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
2018. Vol. 28, no 9, p. 3129-3142
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
Funder
Swedish Research Council, K2014-62X-12190-19-5Forte, Swedish Research Council for Health, Working Life and Welfare, 2009-1709Forte, Swedish Research Council for Health, Working Life and Welfare, 259-2012-23NIH (National Institute of Health), P30 GM103328Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-11-08Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Bazov, IgorSarkisyan, DaniilKononenko, OlgaWatanabe, HiroyukiTaqi, Malik MumtazStålhandske, LadaSyvänen, Ann-ChristineYakovleva, TatianaBakalkin, Georgy

Search in DiVA

By author/editor
Bazov, IgorSarkisyan, DaniilKononenko, OlgaWatanabe, HiroyukiTaqi, Malik MumtazStålhandske, LadaSyvänen, Ann-ChristineYakovleva, TatianaBakalkin, Georgy
By organisation
Department of Pharmaceutical BiosciencesMolecular MedicineScience for Life Laboratory, SciLifeLab
In the same journal
Cerebral Cortex
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf