Activation of the murine type II transforming growth factor-β receptor gene. Up-regulation and function of the transcription factor Elf-3/Ert/Esx/Ese-1

Jae Hwan Kim, Phillip J. Wilder, Jingwen Hou, Tamara Nowling, Angie Rizzino

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Previous studies demonstrated that differentiation of mouse embryonal carcinoma cells leads to transcriptional up-regulation of the mouse type II transforming growth factor-β receptor (mTβR-II) gene. To elucidate the molecular mechanisms regulating transcription of this gene, we isolated the 5′-flanking region of the MTβR-II gene and characterized its expression in F9-differentiated cells. Analysis of MTβR-II promoter/reporter gene constructs demonstrates that two conserved Ets-binding sites play an important role in the activity of the mTβR-II promoter. Importantly, we present evidence that mElf-3, a member of the Ets family, plays a key role in the activation of the mTβR-II promoter. Northern blot analysis reveals that the steady-state levels of mTβR-II mRNA increase in parallel with those of mElf-3 mRNA during the differentiation of F9 embryonal carcinoma cells. We also demonstrate that mElf-3 contains one or more domains that influence its binding to DNA. Finally, we report that a single amino acid substitution in the transactivation domain of mElf-3 reduces its ability to transactivate and elevates its steady-state levels of expression. In conclusion, our data argue that mElf-3 plays a key role in the regulation of the mTβR-II gene, and Elf-3 itself is regulated at multiple levels.

Original languageEnglish (US)
Pages (from-to)17520-17530
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number20
DOIs
StatePublished - May 17 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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