Stimulus-specific hierarchy of enhancer elements within the rat prodynorphin promoter.
Induction of the prodynorphin gene occurs in a tissue-specific manner following different physiological stimuli. Using electrophoretic mobility shift assays, we studied the relative activity of the five major regulatory sites in the rat prodynorphin promoter. Prodynorphin cyclic AMP-responsive element 2 (DynCRE2), DynCRE3, and the noncanonical prodynorphin AP-1 (ncDynAP-1) regulatory sites control, in a coordinated manner, prodynorphin induction in the spinal cord after noxious stimulation, whereas prodynorphin up-regulation in supraoptic neurons is regulated predominantly by the ncDynAP-1. Conversely, prodynorphin transactivation in the ovaries upon gonadotropin stimulation is controlled by DynCRE1 and DynCRE3. Our results support the idea that stimulus-specific changes in nuclear proteins establish a functional hierarchy among regulatory sites in the prodynorphin promoter and provide further insight in the molecular mechanisms that govern prodynorphin gene regulation.
Carrión
A M
AM
Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Mellström
B
B
Luckman
S M
SM
Naranjo
J R
JR
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D004586:Electrophoresis / Q000379:methods; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006062:Gonadotropins / Q000494:pharmacology; D009997:Osmotic Pressure; D010053:Ovary / Q000737:chemistry; D010146:Pain / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000737:chemistry; D013268:Stimulation, Chemical; D013495:Supraoptic Nucleus / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D004745:Enkephalins; D006062:Gonadotropins; D011498:Protein Precursors; D018808:Transcription Factor AP-1; C033660:preproenkephalin; D000242:Cyclic AMP