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J. Biol. Chem., Vol. 277, Issue 20, 17520-17530, May 17, 2002

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Activation of the Murine Type II Transforming Growth Factor- 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, and Angie Rizzino^§

From the Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805

Previous studies demonstrated that differentiation of mouse embryonal carcinoma cells leads to transcriptional up-regulation of the mouse type II transforming growth factor- receptor (mTR-II) gene. To elucidate the molecular mechanisms regulating transcription of this gene, we isolated the 5'-flanking region of the mTR-II gene and characterized its expression in F9-differentiated cells. Analysis of mTR-II promoter/reporter gene constructs demonstrates that two conserved Ets-binding sites play an important role in the activity of the mTR-II promoter. Importantly, we present evidence that mElf-3, a member of the Ets family, plays a key role in the activation of the mTR-II promoter. Northern blot analysis reveals that the steady-state levels of mTR-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 mTR-II gene, and Elf-3 itself is regulated at multiple levels.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF118264.

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