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Brain Res. 2008 Dec 30;1246:1-10. doi: 10.1016/j.brainres.2008.09.083. Epub 2008 Oct 11.

Effects of trichostatin A on neuronal mu-opioid receptor gene expression.

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  • 1Department of Biological Sciences, Seton Hall University, 400 South Orange Ave., South Orange, NJ 07079, USA.

Abstract

In this study, we determined the effects of a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on neuronal mu-opioid receptor (MOR) gene expression using human neuronal NMB cells, endogenously expressing MOR. Recruitment of two classes of HDAC, HDAC1 and HDAC2, to MOR promoter region in situ was detected via chromatin immunoprecipitation (ChIP) analysis with NMB cells. Functional analysis using the luciferase reporter gene system showed that TSA induced an approximately 3-fold increase of the promoter activity as compared to the vehicle treated group. Mutation analysis demonstrated that TSA response was mediated by both dsDNA (Sp1/Sp3 binding site) and ssDNA (PolyC binding protein1, PCBP, binding site) elements located in mouse MOR proximal core promoter region, further suggesting the functional importance of this cis-element, which shows high sequence homology between human and mouse MOR genes. ChIP analysis further suggested that TSA enhanced the recruitment of Sp1/Sp3 and PCBP to the promoter region, whereas no significant changes of total proteins were observed in response to TSA using Western blot analysis. Moreover, confocal images showed TSA-induced nuclear hot spots of endogenous PCBP in neuronal cells, whereas no obvious nuclear PCBP hotspot was observed in vehicle treated cells. Taken together, these results suggested that TSA enhanced neuronal MOR gene expression at the transcriptional level. RT-PCR analysis further revealed that TSA also decreased the steady-state level of MOR mRNA in a time-dependent manner by enhancing its instability. Thus, data suggest that TSA, an epigenetic regulator, affects neuronal MOR gene expression at both transcriptional and post-transcriptional levels.

PMID:
18950606
[PubMed - indexed for MEDLINE]
PMCID:
PMC2639711
Free PMC Article

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