title: Epigenetic regulation of the NR4A orphan nuclear receptor NOR1 by histone acetylation.
abstract: The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We demonstrate that NOR1 transcription is induced by histone deacetylase (HDAC) inhibition and by depletion of HDAC1 and HDAC3. HDAC inhibition activated the NOR1 promoter, increased histone acetylation and augmented the recruitment of phosphorylated CREB to the promoter. Furthermore, HDAC inhibition increased Ser133 phosphorylation of CREB and augmented NOR1 protein stability. These data outline previously unrecognized mechanisms of NOR1 regulation and illustrate a key role for histone acetylation in the rapid induction of NOR1.
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington 40536, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomiyama
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA.
authors.forename: Hannes M
authors.initials: HM
authors.lastname: Findeisen
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington 40536, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Qing
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Aono
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA.
authors.forename: Karrie L
authors.initials: KL
authors.lastname: Jones
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Heywood
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington 40536, USA; Graduate Center for Nutritional Sciences, University of Kentucky, Lexington 40536, USA. Electronic address: Dennis.Bruemmer@uky.edu.
authors.forename: Dennis
authors.initials: D
authors.lastname: Bruemmer
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D055550:Protein Stability / Q000187:drug effects; D051381:Rats
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009419:Nerve Tissue Proteins; C091333:Nr4a3 protein, rat; D057093:Orphan Nuclear Receptors
keywords: Histone deacetylase; Nuclear receptor; Smooth muscle cell