Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/82739
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dc.contributor.authorBersten, D.en
dc.contributor.authorWright, J.en
dc.contributor.authorMcCarthy, P.en
dc.contributor.authorWhitelaw, M.en
dc.date.issued2014en
dc.identifier.citationBiochimica et Biophysica Acta, 2014; 1839(1):13-24en
dc.identifier.issn1874-9399en
dc.identifier.issn1876-4320en
dc.identifier.urihttp://hdl.handle.net/2440/82739-
dc.description.abstractNPAS4 is a brain restricted, activity-induced transcription factor which regulates the expression of inhibitory synapse genes to control homeostatic excitatory/inhibitory balance in neurons. NPAS4 is required for normal social interaction and contextual memory formation in mice. Protein and mRNA expression of NPAS4 is tightly coupled to neuronal depolarization and most prevalent in the cortical and hippocampal regions in the brain, however the precise mechanisms by which the NPAS4 gene is controlled remain unexplored. Here we show that expression of NPAS4 mRNA is actively repressed by RE-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) in embryonic stem cells and non-neuronal cells by binding multiple sites within the promoter and Intron I of NPAS4. Repression by REST also appears to correlate with the binding of the zinc finger DNA binding protein CTCF within Intron I of NPAS4. In addition, we show that the 3' untranslated region (3'UTR) of NPAS4 can be targeted by two microRNAs, miR-203 and miR-224 to further regulate its expression. miR-224 is a midbrain/hypothalamus enriched microRNA which is expressed from an intron within the GABAA receptor epsilon (GABRE) gene and may further regionalize NPAS4 expression. Our results reveal REST and microRNA dependent mechanisms that restrict NPAS4 expression to the brain.en
dc.description.statementofresponsibilityDavid C. Bersten, Josephine A.Wright, Peter J. McCarthy, Murray L.Whitelawen
dc.language.isoenen
dc.publisherElsevier BVen
dc.rightsCrown Copyright © 2013en
dc.subjectGene regulation; NPAS4; REST; microRNA; Transcription factoren
dc.titleRegulation of the neuronal transcription factor NPAS4 by REST and microRNAsen
dc.typeJournal articleen
dc.identifier.rmid0020134075en
dc.identifier.doi10.1016/j.bbagrm.2013.11.004en
dc.identifier.pubid16766-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Molecular and Biomedical Science publications

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