This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakatake, Y.
Right arrow Articles by Niwa, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakatake, Y.
Right arrow Articles by Niwa, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2006, p. 7772-7782, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.00468-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Klf4 Cooperates with Oct3/4 and Sox2 To Activate the Lefty1 Core Promoter in Embryonic Stem Cells{triangledown}

Yuhki Nakatake,1 Nobutaka Fukui,1,2,3 Yuko Iwamatsu,1 Shinji Masui,1 Kadue Takahashi,1 Rika Yagi,1 Kiyohito Yagi,2 Jun-ichi Miyazaki,3 Ryo Matoba,4 Minoru S. H. Ko,4 and Hitoshi Niwa1,5*

Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology (CDB), Minatojima-Minamimachi 2-2-3, Chuo-ku, Kobe 650-0047, Japan,1 Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita C., Osaka 565-0871, Japan,2 Stem Cell Regulation Research, Area of Molecular Therapeutics, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita C., Osaka 565-0871, Japan,3 Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224,4 Laboratory for Development and Regenerative Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan5

Received 17 March 2006/ Returned for modification 2 May 2006/ Accepted 15 August 2006

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.


* Corresponding author. Mailing address: Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Minatojima-Minamimachi 2-2-3, Chu-o-ku, Kobe 650-0047, Japan. Phone: 81-78-306-1927. Fax: 81-78-306-1929. E-mail: niwa{at}cdb.riken.jp.

{triangledown} Published ahead of print on 5 September 2006.


Molecular and Cellular Biology, October 2006, p. 7772-7782, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.00468-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Gao, F., Kwon, S. W., Zhao, Y., Jin, Y. (2009). PARP1 Poly(ADP-ribosyl)ates Sox2 to Control Sox2 Protein Levels and FGF4 Expression during Embryonic Stem Cell Differentiation. J. Biol. Chem. 284: 22263-22273 [Abstract] [Full Text]  
  • Zheng, H., Pritchard, D. M., Yang, X., Bennett, E., Liu, G., Liu, C., Ai, W. (2009). KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol. 296: G490-G498 [Abstract] [Full Text]  
  • Vigneault, C., Gravel, C., Vallee, M., McGraw, S., Sirard, M.-A. (2009). Unveiling the bovine embryo transcriptome during the maternal-to-embryonic transition. Reproduction 137: 245-257 [Abstract] [Full Text]  
  • Chen, X., Vega, V.B., Ng, H.-H. (2008). Transcriptional Regulatory Networks in Embryonic Stem Cells. Cold Spring Harb Symp Quant Biol 0: sqb.2008.73.026v1-sqb.2008.73.026 [Abstract]  
  • van den Berg, D. L. C., Zhang, W., Yates, A., Engelen, E., Takacs, K., Bezstarosti, K., Demmers, J., Chambers, I., Poot, R. A. (2008). Estrogen-Related Receptor Beta Interacts with Oct4 To Positively Regulate Nanog Gene Expression. Mol. Cell. Biol. 28: 5986-5995 [Abstract] [Full Text]  
  • Mise, N., Fuchikami, T., Sugimoto, M., Kobayakawa, S., Ike, F., Ogawa, T., Tada, T., Kanaya, S., Noce, T., Abe, K. (2008). Differences and similarities in the developmental status of embryo-derived stem cells and primordial germ cells revealed by global expression profiling.. GENES CELLS 13: 863-877 [Abstract] [Full Text]  
  • Xie, D., Cai, J., Chia, N.-Y., Ng, H. H., Zhong, S. (2008). Cross-species de novo identification of cis-regulatory modules with GibbsModule: Application to gene regulation in embryonic stem cells. Genome Res 18: 1325-1335 [Abstract] [Full Text]  
  • Yamanaka, S. (2008). Pluripotency and nuclear reprogramming. Phil Trans R Soc B 363: 2079-2087 [Abstract] [Full Text]  
  • Davis, J., Davis, D., Norman, B., Piatigorsky, J. (2008). Gene Expression of the Mouse Corneal Crystallin Aldh3a1: Activation by Pax6, Oct1, and p300. IOVS 49: 1814-1826 [Abstract] [Full Text]  
  • Alder, J. K., Georgantas, R. W. III, Hildreth, R. L., Kaplan, I. M., Morisot, S., Yu, X., McDevitt, M., Civin, C. I. (2008). Kruppel-Like Factor 4 Is Essential for Inflammatory Monocyte Differentiation In Vivo. J. Immunol. 180: 5645-5652 [Abstract] [Full Text]  
  • Niwa, H. (2007). Open conformation chromatin and pluripotency. Genes Dev. 21: 2671-2676 [Full Text]  
  • Behr, R., Deller, C., Godmann, M., Muller, T., Bergmann, M., Ivell, R., Steger, K. (2007). Kruppel-like factor 4 expression in normal and pathological human testes. Mol Hum Reprod 13: 815-820 [Abstract] [Full Text]  
  • Atkins, G. B., Jain, M. K. (2007). Role of Kruppel-Like Transcription Factors in Endothelial Biology. Circ. Res. 100: 1686-1695 [Abstract] [Full Text]  
  • Boer, B., Kopp, J., Mallanna, S., Desler, M., Chakravarthy, H., Wilder, P. J., Bernadt, C., Rizzino, A. (2007). Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes. Nucleic Acids Res 0: gkm059v2-14 [Abstract] [Full Text]  
  • Niwa, H. (2007). How is pluripotency determined and maintained?. Development 134: 635-646 [Abstract] [Full Text]