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Scientific article
English

Negative elongation factor NELF controls transcription of immediate early genes in a stimulus-specific manner

Contributors

Fujita, Toshitsugu; Piuz, Isabelle; Schlegel, Werner

Published in

Experimental cell research, vol. 315, no. 2, p. 274-284

Publication date

2009

Abstract

The transcription rate of immediate early genes (IEGs) is controlled directly by transcription elongation factors at the transcription elongation step. Negative elongation factor (NELF) and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) stall RNA polymerase II (pol II) soon after transcription initiation. Upon induction of IEG transcription, DSIF is converted into an accelerator for pol II elongation. To address whether and how NELF as well as DSIF controls overall IEG transcription, its expression was reduced using stable RNA interference in GH4C1 cells. NELF knock-down reduced thyrotropin-releasing hormone (TRH)-induced transcription of the IEGs c-fos, MKP-1, and junB. In contrast, epidermal growth factor (EGF)-induced transcription of these IEGs was unaltered or even slightly increased by NELF knock-down. Thus, stable knock-down of NELF affects IEG transcription stimulation-specifically. Conversely, DSIF knock-down reduced both TRH- and EGF-induced transcription of the three IEGs. Interestingly, TRH-induced activation of the MAP kinase pathway, a pathway essential for transcription of the three IEGs, was down-regulated by NELF knock-down. Thus, stable knock-down of NELF, by modulating intracellular signaling pathways, caused stimulation-specific loss of IEG transcription. These observations indicate that NELF controls overall IEG transcription via multiple mechanisms both directly and indirectly.

Keywords

  • 5' Untranslated Regions/genetics
  • Animals
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Chromosomal Proteins, Non-Histone/genetics/metabolism
  • Dual Specificity Phosphatase 1/genetics/metabolism
  • Epidermal Growth Factor/pharmacology
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Gene Expression Regulation, Neoplastic/drug effects/genetics
  • Genes, Immediate-Early/genetics
  • MAP Kinase Signaling System/drug effects
  • Nerve Tissue Proteins/physiology
  • Phosphorylation/drug effects
  • Potassium Chloride/pharmacology
  • Protein Binding
  • Proto-Oncogene Proteins c-fos/genetics/metabolism
  • Proto-Oncogene Proteins c-jun/genetics/metabolism
  • RNA, Small Interfering/genetics
  • Rats
  • Thyrotropin-Releasing Hormone/pharmacology
  • Transcriptional Elongation Factors/genetics/metabolism
  • Tumor Necrosis Factor-alpha/pharmacology

UNIGE affiliation entities

Citation (ISO format)

FUJITA, Toshitsugu, PIUZ, Isabelle, SCHLEGEL, Werner. Negative elongation factor NELF controls transcription of immediate early genes in a stimulus-specific manner. In: Experimental cell research, 2009, vol. 315, n° 2, p. 274–284. doi: 10.1016/j.yexcr.2008.10.032

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

0014-4827
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Technical informations

Creation

31/03/2009 15:51:00

First validation

31/03/2009 15:51:00

Update

26/03/2026 10:41:54

Status update

26/03/2026 10:41:54

Last indexation

26/03/2026 10:47:04
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