title: C/EBP activates the human corticotropin-releasing hormone gene promoter.
abstract: The purpose of these studies was to identify whether transcription factors, associated with cytokine signalling, affected promoter activity of the corticotropin releasing hormone (CRH) gene. Fragments of a 3.6 kb sequence of the human CRH gene promoter were amplified by PCR and ligated upstream of a CAT reporter. These constructs were transfected into a variety of cell lines, either alone or together, with transcription factor expression vectors. Basal activity of a 3070 bp CRH promoter fragment was only seen in neuronal and lymphoblastoid cell lines. Promoter activity was increased by the transcription factors C/EBPbeta (NF-IL6) and more strongly, by C/EBPdelta (NF-IL6beta). Increased CRH promoter activity following phorbol ester treatment was inhibited by a dominant negative NF-IL6 mutant, showing that the effects of phorbol ester were principally mediated by C/EBP. Moreover, the inverse changes in the expression of CRH in the hypothalamus and spleens of arthritic rats were paralleled by similar inverse changes in NF-IL6beta expression in these organs. These data show that some transcription factors associated with cytokine signalling can also activate the CRH promoter.
authors.affiliation: Department of Molecular Pathology, University College London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Stephanou
authors.forename: A
authors.initials: A
authors.lastname: Okosi
authors.forename: R A
authors.initials: RA
authors.lastname: Knight
authors.forename: H S
authors.initials: HS
authors.lastname: Chowdrey
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008214:Lymphocytes; D008297:Male; D009000:Monocytes; D009154:Mutation; D009474:Neurons; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D013154:Spleen / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D003346:Corticotropin-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate