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Title

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

Authors
Maisonnasse-Charital, Ysadora
van Haasteren, Goedele
Published in Gene. 2009, vol. 430, no. 1-2, p. 116-22
Abstract 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.
Keywords AnimalsBase SequenceEnhancer Elements, Genetic/geneticsGene Expression Regulation/drug effectsIntrons/geneticsMiceMolecular Sequence DataNF-kappa B/metabolismProtein Binding/drug effectsProto-Oncogene Proteins c-fos/genetics/metabolismRatsSignal Transduction/drug effectsThyrotropin-Releasing Hormone/pharmacologyTranscription, Genetic/drug effectsTumor Necrosis Factor-alpha/pharmacology
Stable URL http://archive-ouverte.unige.ch/unige:1272
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Identifiers
PMID: 19026727
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Deposited on : 2009-03-31

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