PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.

The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.
AuthorsRichard Henriksson, Cristina M Bäckman, Brandon K Harvey, Helena Kadyrova, Igor Bazov, Toni S Shippenberg, Georgy Bakalkin
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1839 Issue 11 Pg. 1226-32 (Nov 2014) ISSN: 0006-3002 [Print] Netherlands
PMID25220237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Enkephalins
  • MIRN92 microRNA, human
  • MicroRNAs
  • Protein Precursors
  • RE1-silencing transcription factor
  • Repressor Proteins
  • preproenkephalin
  • Adult
  • Brain (metabolism, pathology)
  • Cells, Cultured
  • Embryonic Stem Cells (metabolism)
  • Enkephalins (genetics, metabolism)
  • Gene Expression Regulation
  • Humans
  • Mental Disorders (genetics, metabolism, pathology)
  • MicroRNAs (physiology)
  • Neurons (metabolism, pathology)
  • Protein Precursors (genetics, metabolism)
  • Repressor Proteins (physiology)

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