Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1

Hong-Mei Zhang1, Li Li, Nektaria Papadopoulou

  • 1Centre for Biochemistry and Cell Biology, and School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.

Nucleic Acids Research
|March 13, 2008
PubMed

Insights

Extracellular signals regulate genes via the c-fos serum response element (SRE). Mitogen-activated protein kinases (MAPKs), including ERK and MSK, are recruited to SRE promoter complexes, influencing transcription initiation.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cell Signaling

Background:

  • Eukaryotic gene expression is tightly controlled by extracellular signals.
  • The c-fos serum response element (SRE) is crucial for transcriptional activation mediated by serum response factor (SRF) and Elk-1.
  • The precise mechanisms by which promoter-bound factors stimulate transcription initiation remain incompletely understood.

Purpose of the Study:

  • To investigate the recruitment of specific mitogen-activated protein kinases (MAPKs) to SRE promoter complexes.
  • To elucidate the role of these MAPKs in the transcriptional activation of acutely regulated genes.

Main Methods:

  • In vitro and in vivo recruitment assays for ERK and MSK to SRE promoter complexes.
  • Analysis of Elk-1 binding domain interactions with ERK.
  • Assessment of histone H3 phosphorylation and RNA polymerase II association.
  • Elk-1 knockdown experiments.

Main Results:

  • ERK and MSK kinases are recruited to SRE promoter complexes.
  • ERK recruitment involves the D domain/KIM of Elk-1.
  • In vivo recruitment is mitogen-stimulated, correlates with histone H3 phosphorylation, and depends on Elk-1.
  • ERK associates with initiating RNA polymerase II.

Conclusions:

  • ERK and MSK kinases play a role in the recruitment of transcription machinery to SRE promoters.
  • These findings suggest a broader role for ERK and related MAPKs in the regulation of acutely responsive genes.

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