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 Tokuzawa, Y.
Right arrow Articles by Yamanaka, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tokuzawa, Y.
Right arrow Articles by Yamanaka, S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2003, p. 2699-2708, Vol. 23, No. 8
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.8.2699-2708.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Fbx15 Is a Novel Target of Oct3/4 but Is Dispensable for Embryonic Stem Cell Self-Renewal and Mouse Development

Yoshimi Tokuzawa,1 Eiko Kaiho,1 Masayoshi Maruyama,1 Kazutoshi Takahashi,1 Kaoru Mitsui,1 Mitsuyo Maeda,2 Hitoshi Niwa,3 and Shinya Yamanaka1*

Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630-0192,1 First Department of Anatomy, Osaka City University Medical School, Osaka 545-8585,2 Laboratory of Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan3

Received 8 August 2002/ Returned for modification 1 November 2002/ Accepted 19 December 2002

Embryonic stem (ES) cells are immortal and pluripotent cells derived from early mammalian embryos. Transcription factor Oct3/4 is essential for self-renewal of ES cells and early mouse development. However, only a few Oct3/4 target genes have been identified. In this study, we found that F-box-containing protein Fbx15 was expressed predominantly in mouse undifferentiated ES cells. Inactivation of Oct3/4 in ES cells led to rapid extinction of Fbx15 expression. Reporter gene analyses demonstrated that this ES cell-specific expression required an 18-bp enhancer element located approximately 500 nucleotides upstream from the transcription initiation site. The enhancer contained an octamer-like motif and an adjacent Sox-binding motif. Deletion or point mutation of either motif abolished the enhancer activity. The 18-bp fragment became active in NIH 3T3 cells when Oct3/4 and Sox2 were coexpressed. A gel mobility shift assay demonstrated cooperative binding of Oct3/4 and Sox2 to the enhancer sequence. In mice having a ß-galactosidase gene knocked into the Fbx15 locus, 5-bromo-4-chloro-3-indolyl-ß-D-galactopyranoside staining was detected in ES cells, early embryos (two-cell to blastocyst stages), and testis tissue. Despite such specific expression of Fbx15, homozygous mutant mice showed no gross developmental defects and were fertile. Fbx15-null ES cells were normal in morphology, proliferation, and differentiation. These data demonstrate that Fbx15 is a novel target of Oct3/4 but is dispensable for ES cell self-renewal, development, and fertility.

* Corresponding author. Mailing address: Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630-0101, Japan. Phone: 81-743-72-5591. Fax: 81-743-72-5599. E-mail: shinyay{at}gtc.aist-nara.ac.jp.

Molecular and Cellular Biology, April 2003, p. 2699-2708, Vol. 23, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.8.2699-2708.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tsubooka, N., Ichisaka, T., Okita, K., Takahashi, K., Nakagawa, M., Yamanaka, S. (2009). Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts. GENES CELLS 14: 683-694 [Abstract] [Full Text]  
  • Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., Yamanaka, S. (2008). Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors. Science 322: 949-953 [Abstract] [Full Text]  
  • Greer Card, D. A., Hebbar, P. B., Li, L., Trotter, K. W., Komatsu, Y., Mishina, Y., Archer, T. K. (2008). Oct4/Sox2-Regulated miR-302 Targets Cyclin D1 in Human Embryonic Stem Cells. Mol. Cell. Biol. 28: 6426-6438 [Abstract] [Full Text]  
  • Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T., Yamanaka, S. (2008). Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells. Science 321: 699-702 [Abstract] [Full Text]  
  • Yamanaka, S. (2008). Pluripotency and nuclear reprogramming. Phil Trans R Soc B 363: 2079-2087 [Abstract] [Full Text]  
  • Perrett, R. M., Turnpenny, L., Eckert, J. J., O'Shea, M., Sonne, S. B., Cameron, I. T., Wilson, D. I., Meyts, E. R.-D., Hanley, N. A. (2008). The Early Human Germ Cell Lineage Does Not Express SOX2 During In Vivo Development or upon In Vitro Culture. Biol. Reprod. 78: 852-858 [Abstract] [Full Text]  
  • Lavial, F., Acloque, H., Bertocchini, F., MacLeod, D. J., Boast, S., Bachelard, E., Montillet, G., Thenot, S., Sang, H. M., Stern, C. D., Samarut, J., Pain, B. (2007). The Oct4 homologue PouV and Nanog regulate pluripotency in chicken embryonic stem cells. Development 134: 3549-3563 [Abstract] [Full Text]  
  • Wang, Z.-X., Teh, C. H.-L., Kueh, J. L. L., Lufkin, T., Robson, P., Stanton, L. W. (2007). Oct4 and Sox2 Directly Regulate Expression of Another Pluripotency Transcription Factor, Zfp206, in Embryonic Stem Cells. J. Biol. Chem. 282: 12822-12830 [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]  
  • Uemoto, Y., Suzuki, S.-i., Terada, N., Ohno, N., Ohno, S., Yamanaka, S., Komada, M. (2007). Specific Role of the Truncated betaIV-Spectrin {Sigma}6 in Sodium Channel Clustering at Axon Initial Segments and Nodes of Ranvier. J. Biol. Chem. 282: 6548-6555 [Abstract] [Full Text]  
  • Niwa, H. (2007). How is pluripotency determined and maintained?. Development 134: 635-646 [Abstract] [Full Text]  
  • Pereira, L., Yi, F., Merrill, B. J. (2006). Repression of Nanog Gene Transcription by Tcf3 Limits Embryonic Stem Cell Self-Renewal. Mol. Cell. Biol. 26: 7479-7491 [Abstract] [Full Text]  
  • 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. Mol. Cell. Biol. 26: 7772-7782 [Abstract] [Full Text]  
  • Takahashi, K., Nakagawa, M., Young, S. G., Yamanaka, S. (2005). Differential Membrane Localization of ERas and Rheb, Two Ras-related Proteins Involved in the Phosphatidylinositol 3-Kinase/mTOR Pathway. J. Biol. Chem. 280: 32768-32774 [Abstract] [Full Text]  
  • Chew, J.-L., Loh, Y.-H., Zhang, W., Chen, X., Tam, W.-L., Yeap, L.-S., Li, P., Ang, Y.-S., Lim, B., Robson, P., Ng, H.-H. (2005). Reciprocal Transcriptional Regulation of Pou5f1 and Sox2 via the Oct4/Sox2 Complex in Embryonic Stem Cells. Mol. Cell. Biol. 25: 6031-6046 [Abstract] [Full Text]  
  • Maruyama, M., Ichisaka, T., Nakagawa, M., Yamanaka, S. (2005). Differential Roles for Sox15 and Sox2 in Transcriptional Control in Mouse Embryonic Stem Cells. J. Biol. Chem. 280: 24371-24379 [Abstract] [Full Text]  
  • Rodda, D. J., Chew, J.-L., Lim, L.-H., Loh, Y.-H., Wang, B., Ng, H.-H., Robson, P. (2005). Transcriptional Regulation of Nanog by OCT4 and SOX2. J. Biol. Chem. 280: 24731-24737 [Abstract] [Full Text]  
  • Nishimoto, M., Miyagi, S., Yamagishi, T., Sakaguchi, T., Niwa, H., Muramatsu, M., Okuda, A. (2005). Oct-3/4 Maintains the Proliferative Embryonic Stem Cell State via Specific Binding to a Variant Octamer Sequence in the Regulatory Region of the UTF1 Locus. Mol. Cell. Biol. 25: 5084-5094 [Abstract] [Full Text]  
  • Kuroda, T., Tada, M., Kubota, H., Kimura, H., Hatano, S.-y., Suemori, H., Nakatsuji, N., Tada, T. (2005). Octamer and Sox Elements Are Required for Transcriptional cis Regulation of Nanog Gene Expression. Mol. Cell. Biol. 25: 2475-2485 [Abstract] [Full Text]  
  • Okumura-Nakanishi, S., Saito, M., Niwa, H., Ishikawa, F. (2005). Oct-3/4 and Sox2 Regulate Oct-3/4 Gene in Embryonic Stem Cells. J. Biol. Chem. 280: 5307-5317 [Abstract] [Full Text]  
  • O'Shea, K. S. (2004). Self-renewal vs. Differentiation of Mouse Embryonic Stem Cells. Biol. Reprod. 71: 1755-1765 [Abstract] [Full Text]  
  • Murakami, M., Ichisaka, T., Maeda, M., Oshiro, N., Hara, K., Edenhofer, F., Kiyama, H., Yonezawa, K., Yamanaka, S. (2004). mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells. Mol. Cell. Biol. 24: 6710-6718 [Abstract] [Full Text]  
  • Miyagi, S., Saito, T., Mizutani, K.-i., Masuyama, N., Gotoh, Y., Iwama, A., Nakauchi, H., Masui, S., Niwa, H., Nishimoto, M., Muramatsu, M., Okuda, A. (2004). The Sox-2 Regulatory Regions Display Their Activities in Two Distinct Types of Multipotent Stem Cells. Mol. Cell. Biol. 24: 4207-4220 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»