التفاصيل البيبلوغرافية
| العنوان: |
Multiple ETS Family Proteins Regulate PF4 Gene Expression by Binding to the Same ETS Binding Site. |
| المؤلفون: |
Okada, Yoshiaki, Nobori, Haruaki, Shimizu, Mikiko, Watanabe, Miho, Yonekura, Masaaki, Nakai, Tomoko, Kamikawa, Yuko, Wakimura, Atsuko, Funahashi, Nobuaki, Naruse, Hiroki, Watanabe, Ayako, Yamasaki, Daisuke, Fukada, So-ichiro, Yasui, Kazuta, Matsumoto, Kayoko, Sato, Takahiro, Kitajima, Kenji, Nakano, Toru, Aird, William C., Doi, Takefumi |
| المصدر: |
PLoS ONE; 2011, Vol. 6 Issue 9, p1-10, 10p |
| مصطلحات موضوعية: |
MOLECULAR biology, GENE expression, MEGAKARYOCYTES, RADIOLIGAND assay, TRANSCRIPTION factors, PROMOTERS (Genetics), PROTEIN binding, SMALL interfering RNA |
| مستخلص: |
In previous studies on the mechanism underlying megakaryocyte-specific gene expression, several ETS motifs were found in each megakaryocyte-specific gene promoter. Although these studies suggested that several ETS family proteins regulate megakaryocyte-specific gene expression, only a few ETS family proteins have been identified. Platelet factor 4 (PF4) is a megakaryocyte-specific gene and its promoter includes multiple ETS motifs. We had previously shown that ETS-1 binds to an ETS motif in the PF4 promoter. However, the functions of the other ETS motifs are still unclear. The goal of this study was to investigate a novel functional ETS motif in the PF4 promoter and identify proteins binding to the motif. In electrophoretic mobility shift assays and a chromatin immunoprecipitation assay, FLI-1, ELF-1, and GABP bound to the -51 ETS site. Expression of FLI-1, ELF-1, and GABP activated the PF4 promoter in HepG2 cells. Mutation of a -51 ETS site attenuated FLI- 1-, ELF-1-, and GABP-mediated transactivation of the promoter. siRNA analysis demonstrated that FLI-1, ELF-1, and GABP regulate PF4 gene expression in HEL cells. Among these three proteins, only FLI-1 synergistically activated the promoter with GATA-1. In addition, only FLI-1 expression was increased during megakaryocytic differentiation. Finally, the importance of the -51 ETS site for the activation of the PF4 promoter during physiological megakaryocytic differentiation was confirmed by a novel reporter gene assay using in vitro ES cell differentiation system. Together, these data suggest that FLI- 1, ELF-1, and GABP regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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