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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2027-2034. Prepublished online as a Blood First Edition Paper on June 8, 2004; DOI 10.1182/blood-2003-09-3107. This Article Full Text (PDF) All Versions of this Article: 2003-09-3107v1 104/7/2027    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Okada, Y. Articles by Doi, T. Search for Related Content PubMed PubMed Citation Articles by Okada, Y. Articles by Doi, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 10, 2003 Accepted May 16, 2004 Upstream stimulatory factors stimulate transcription through the E-box motifs in the PF4 gene in megakaryocytes Yoshiaki Okada, Eri Matsuura, Zenzaburo Tozuka, Ryohei Nagai, Ayako Watanabe, Kayoko Matsumoto, Kazuta Yasui, Robert W Jackman, Toru Nakano, and Takefumi Doi* Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan Biopharmaceutical and Pharmacokinetics Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Yodogawa-ku, Osaka, Japan Osaka Red Cross Blood Center, Johtoh-ku, Osaka, Japan Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA, USA Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Graduate School of Medicine, Osaka University, Suita, Osaka, Japan Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan; Graduate School of Medicine, Osaka University, Suita, Osaka, Japan * Corresponding author; email: doi{at}phs.osaka-u.ac.jp. Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We previously demonstrated that the homeodomain proteins (MEIS1, PREP1 and PBXs) bind to the novel regulatory element (TME) and transactivate the rat PF4 promoter. In the present study, we investigated and identified other TME binding proteins in megakaryocytic HEL cells using mass spectrometry. Among identified proteins, we focused on upstream stimulatory factor (USF) 1 and 2 and investigated their effects on the PF4 promoter. USF1 and 2 bound to the E-box motif in the TME and strongly transactivated the PF4 promoter. Furthermore, physiological bindings of USF1 and 2 to the TME in rat megakaryocytes were demonstrated by the Chromatin Immunoprecipitation (ChIP) assay. Interestingly, the E-box motif in the TME was conserved in TME-like sequences of both the human and mouse PF4 promoters. USF1 and 2 also bound to the human TME-like sequence and transactivated the human PF4 promoter. Expressions of USF1 and 2 were detected by RT-PCR in the human megakaryocytes derived from CD34+ cells. Thus, these studies demonstrate that the novel TME binding transcription factors, USF1 and 2, transactivate rat and human PF4 promoters and may play an important role in megakaryocytic gene expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Sayasith, J. G. Lussier, and J. Sirois Role of Upstream Stimulatory Factor Phosphorylation in the Regulation of the Prostaglandin G/H Synthase-2 Promoter in Granulosa Cells J. Biol. Chem., August 12, 2005; 280(32): 28885 - 28893. [Abstract] [Full Text] [PDF]

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