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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Gene Expression Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Upstream stimulatory factors stimulate transcription through 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 From the Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; the Biopharmaceutical and Pharmacokinetics Research Laboratories, Fujisawa Pharmaceutical, Osaka, Japan; the Osaka Red Cross Blood Center, Osaka, Japan; Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA; the Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and the Graduate School of Medicine, Osaka University, Osaka, Japan. Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We previously demonstrated that the homeodomain proteins (myeloid ecotropic integra tion site 1 [MEIS1], Pbx-regulating protein 1 [PREP1], and pre-B-cell leukemia transcription factors [PBXs]) bind to the novel regulatory element tandem repeat of MEIS1 binding 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 (USF1) and USF2 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, physiologic 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 reverse-transcriptase–polymerase chain reaction (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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