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

• Published in: Biochimica et biophysica acta 2014-11, Vol.1839 (11), p.1226-1232
• Main Authors: Henriksson, Richard, Bäckman, Cristina M., Harvey, Brandon K., Kadyrova, Helena, Bazov, Igor, Shippenberg, Toni S., Bakalkin, Georgy
• Format: Article
• Language: English
• Subjects: Adult; Brain - metabolism; Brain - pathology; Cells, Cultured; Embryonic Stem Cells - metabolism; Enkephalins - genetics; Enkephalins - metabolism; Gene Expression Regulation; Humans; Medicin och hälsovetenskap; Mental Disorders - genetics; Mental Disorders - metabolism; Mental Disorders - pathology; MicroRNAs - physiology; MIR-9; Neurons - metabolism; Neurons - pathology; NRSF; PDYN; Prefrontal cortex; Protein Precursors - genetics; Protein Precursors - metabolism; Repressor Proteins - physiology; REST; SH-SY5Y cell
• ISSN: 1874-9399; 0006-3002; 1878-2434; 1876-4320; 1878-2434
• DOI: 10.1016/j.bbagrm.2014.09.001

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. •We study transcriptional control of PDYN in SH-SY5Y cells and the human brain.•We determine the REST-PDYN binding profile in SH-SY5Y cells and the human brain.•Interfering with REST activity results in increased PDYN expression in SH-SY5Y cells.•Reduced REST binding coincides with higher PDYN expression in the human brain.•REST represses PDYN expression in both SH-SY5Y cells and the human brain.