Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells

Yuhki Nakatake, Nobutaka Fukui, Yuko Iwamatsu, Shinji Masui, Kadue Takahashi, Rika Yagi, Kiyohito Yagi, Jun Ichi Miyazaki, Ryo Matoba, Minoru S.H. Ko, Hitoshi Niwa

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191 Citations (Scopus)

Abstract

Although the POU transcription factor Oct3/4 is pivotal in maintaining self renewal of embryonic stem (ES) cells, little is known of its molecular mechanisms. We previously reported that the N-terminal transactivation domain of Oct3/4 is required for activation of Lefty1 expression (H. Niwa, S. Masui, I. Chambers, A. G. Smith, and J. Miyazaki, Mol. Cell. Biol. 22:1526-1536, 2002). Here we test whether Lefty1 is a direct target of Oct3/4. We identified an ES cell-specific enhancer upstream of the Lefty1 promoter that contains binding sites for Oct3/4 and Sox2. Unlike other known Oct3/4-Sox2-dependent enhancers, however, this enhancer element could not be activated by Oct3/4 and Sox2 in differentiated cells. By functional screening of ES-specific transcription factors, we found that Krüppel-like factor 4 (Klf4) cooperates with Oct3/4 and Sox2 to activate Lefty1 expression, and that Klf4 acts as a mediating factor that specifically binds to the proximal element of the Lefty1 promoter. DNA microarray analysis revealed that a subset of putative Oct3/4 target genes may be regulated in the same manner. Our findings shed light on a novel function of Oct3/4 in ES cells.

Original languageEnglish
Pages (from-to)7772-7782
Number of pages11
JournalMolecular and Cellular Biology
Volume26
Issue number20
DOIs
Publication statusPublished - 2006 Oct 1

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Nakatake, Y., Fukui, N., Iwamatsu, Y., Masui, S., Takahashi, K., Yagi, R., Yagi, K., Miyazaki, J. I., Matoba, R., Ko, M. S. H., & Niwa, H. (2006). Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Molecular and Cellular Biology, 26(20), 7772-7782. https://doi.org/10.1128/MCB.00468-06