RGD Reference Report - Evidence of the neuron-restrictive silencer factor (NRSF) interaction with Sp3 and its synergic repression to the mu opioid receptor (MOR) gene. - Rat Genome Database

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Evidence of the neuron-restrictive silencer factor (NRSF) interaction with Sp3 and its synergic repression to the mu opioid receptor (MOR) gene.

Authors: Kim, CS  Choi, HS  Hwang, CK  Song, KY  Lee, BK  Law, PY  Wei, LN  Loh, HH 
Citation: Kim CS, etal., Nucleic Acids Res. 2006;34(22):6392-403. Epub 2006 Nov 27.
RGD ID: 8553999
Pubmed: PMID:17130167   (View Abstract at PubMed)
PMCID: PMC1702488   (View Article at PubMed Central)
DOI: DOI:10.1093/nar/gkl724   (Journal Full-text)

Previously, we reported that the neuron-restrictive silencer element (NRSE) of mu opioid receptor (MOR) functions as a critical regulator to repress the MOR transcription in specific neuronal cells, depending on neuron-restriction silence factor (NRSF) expression levels [C.S.Kim, C.K.Hwang, H.S.Choi, K.Y.Song, P.Y.Law, L.N. Wei and H.H.Loh (2004) J. Biol. Chem., 279, 46464-46473]. Herein, we identify a conserved GC sequence next to NRSE region in the mouse MOR gene. The inhibition of Sp family factors binding to this GC box by mithramycin A led to a significant increase in the endogenous MOR transcription. In the co-immunoprecipitation experiment, NRSF interacted with the full-length Sp3 factor, but not with Sp1 or two short Sp3 isoforms. The sequence specific and functional binding by Sp3 at this GC box was confirmed by in vitro gel-shift assays using either in vitro translated proteins or nuclear extract, and by in vivo chromatin immunoprecipitation assays. Transient transfection assays showed that Sp3-binding site of the MOR gene is a functionally synergic repressor element with NRSE in NS20Y cells, but not in the NRSF negative PC12 cells. The results suggest that the synergic interaction between NRSF and Sp3 is required to negatively regulate MOR gene transcription and that transcription of MOR gene would be governed by the context of available transcription factors rather than by a master regulator.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RestRatnegative regulation of DNA-templated transcription involved_inIDA PMID:17130167UniProt 
Sp3Ratnegative regulation of DNA-templated transcription involved_inIDA PMID:17130167UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RestRattranscription repressor complex part_ofIDA PMID:17130167UniProt 
Sp3Rattranscription repressor complex part_ofIDA PMID:17130167UniProt 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Rest  (RE1-silencing transcription factor)
Sp3  (Sp3 transcription factor)


Additional Information