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Scientific article
English

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

Contributors

Maisonnasse-Charital, Ysadora; van Haasteren, Goedele; Massiha, Abbas; Schlegel, Werner; Fujita, Toshitsugu

Published in

Gene, vol. 430, no. 1-2, p. 116-122

Publication date

2009

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

  • 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

UNIGE affiliation entities

Citation (ISO format)

MAISONNASSE-CHARITAL, Ysadora et al. A functional NF-kappaB enhancer element in the first intron contributes to the control of c-fos transcription. In: Gene, 2009, vol. 430, n° 1-2, p. 116–122. doi: 10.1016/j.gene.2008.10.014

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

0378-1119
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3downloads

Technical informations

Creation

31/03/2009 16:12:00

First validation

31/03/2009 16:12:00

Update

26/03/2026 10:41:49

Status update

26/03/2026 10:41:49

Last indexation

26/03/2026 10:47:00
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