title: Coactivator CBP in the regulation of conceptus IFNtau gene transcription.
abstract: Studies of ovine interferon-tau (oIFNtau) 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 oIFNtau gene were identified; however, a molecular mechanism by which these factors regulate oIFNtau 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 oIFNtau gene transcription in a transient transfection system using human choriocarcinoma JEG3 cells. The oIFNtau 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 oIFNtau-reporter construct; however, this coactivator had no effect on the oIFNtau-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 oIFNtau 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 (Delta2-36), suppressed oIFNtau gene transcription. These observations suggest that c-jun and Ets-2 are the most probable binding partners for CBP in the potentiation of oIFNtau gene transcription. Mol. Reprod. Dev. 65: 23-29, 2003.
authors.affiliation: Laboratory of Animal Breeding, Faculty of Agriculture, The University of Tokyo, Yayoi, Bunkyo-ku, Japan.
authors.forename: Ningchun
authors.initials: N
authors.lastname: Xu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Fuko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Senkiti
authors.initials: S
authors.lastname: Sakai
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Christenson
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
mesh_terms: D002822:Choriocarcinoma / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; D007370:Interferon Type I; D011257:Pregnancy Proteins; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C020947:interferon tau; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases