A functional NF-kappaB enhancer element in the first intron contributes to the control of c-fos transcription

Article Article scientifique Article A functional NF-kappaB enhancer element in the first intron contributes to the control of c-fos transcription eng 2009 author Maisonnasse-Charital Ysadora author van Haasteren Goedele author Massiha Abbas 128089 author Schlegel Werner 26447 author Fujita Toshitsugu 601737 116-122 10.1016/j.gene.2008.10.014 19026727 0378-1119 Eukaryotic gene transcription is controlled not only by gene promoters but also by intragenic cis-elements. Such regulation is important for the transcription of immediate early genes (IEGs) and in particular for the c-fos gene, the first intron of which contains many potential transcription factor binding elements. In the present study, we addressed the intronic control of c-fos transcription by the NF-kappaB signalling pathway in the neuroendocrine cell line GH4C1. Tumour necrosis factor alpha (TNFalpha) activating the NF-kappaB signalling pathway induced transcription of the c-fos gene and enhanced thyrotropin-releasing hormone-stimulated (TRH-stimulated) c-fos transcription. To examine the effects of NF-kappaB, the presumed NF-kappaB binding sequence in the first intron was mutated or deleted from c-fos reporter gene constructs. When GH4C1 cells transfected with the reporter constructs were stimulated by TNFalpha, the induced expression was significantly diminished. Double-stranded short DNA with the intronic NF-kappaB binding consensus sequence interacted directly with NF-kappaB p50 protein in vitro; mutation of 3 nucleotides destroying the consensus abolished the in vitro interaction. The importance of NF-kappaB for c-fos expression was also supported by RNA interference experiments; knock-down of NF-kappaB p50 suppressed TNFalpha-induced c-fos expression. In addition, chromatin immunoprecipitation indicated that NF-kappaB occupied the first intron of the c-fos gene in vivo. In conclusion, NF-kappaB enhances c-fos transcription via the direct binding to a response element situated in the first intron. Animals Base Sequence Enhancer Elements, Genetic/genetics Gene Expression Regulation/drug effects Introns/genetics Mice Molecular Sequence Data NF-kappa B/metabolism Protein Binding/drug effects Proto-Oncogene Proteins c-fos/genetics/metabolism Rats Signal Transduction/drug effects Thyrotropin-Releasing Hormone/pharmacology Transcription, Genetic/drug effects Tumor Necrosis Factor-alpha/pharmacology Dewey 616 56 Département de médecine 221 false Gene 430 1-2 050e7082-aba9-43e2-804c-ff6f887dbf2e Article (Accepted version) Restricted Article.pdf 704069 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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A functional NF-kappaB enhancer element in the first intron contributes to the control of c-fos transcription	Gene			2009	622	3

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Massiha, Abbas