Coactivator CBP in the Regulation of Conceptus IFNtau Gene Transcription
2003
Xu, Ningchun | Takahashi, Yuji | Matsuda, Fuko | Sakai, Senkiti | Christenson, Ronald K. | Imakawa, Kazuhiko
Studies of ovine interferon-tau (oIFN) gene regulation, an anti-luteolytic factor produced by conceptuses of the ruminant ungulates, have been carried out, but a definitive mechanism for its spatial-temporal transcription has not been elucidated. Recently, specific binding regions for transcription factors AP-1 and Ets-2 on the oIFN gene were identified; however, a molecular mechanism by which these factors regulate oIFN gene transcription has not been characterized. In the present study, we investigated the potential relationship between AP-1 and Ets-2, and their association with a coactivator, cAMP-response element binding protein-binding protein (CBP), on oIFN gene transcription in a transient transfection system using human choriocarcinoma JEG3 cells. The oIFN gene promoter/enhancer (-654 to + 1 bases, wild type)-luciferase reporter construct (pGL3-654) or its mutant at the AP-1 or Ets-2 site was cotransfected with CBP (pRc/RSV-CBP) construct along with c-jun, c-fos, and/or Ets-2 expression plasmid. CBP enhanced transcription of the wild type oIFN-reporter construct; however, this coactivator had no effect on the oIFN-reporter construct with mutated AP-1 or Ets-2 site. Cotransfection of CBP with c-jun and/or Ets-2, but not with c-fos, further increased oIFN gene transactivation although amounts of c-jun and c-fos expression, resulting from expression vectors, were similar. In addition, CBP inhibitor adenovirus 12S E1A (E1A), but not the mutant of E1A without CBP binding domain (delta 2-36), suppressed oIFN gene transcription. These observations suggest that c-jun and Ets-2 are the most probable binding partners for CBP in the potentiation of oIFN gene transcription.
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