Coactivator CBP in the regulation of conceptus IFNtau gene transcription

Mol Reprod Dev. 2003 May;65(1):23-9. doi: 10.1002/mrd.10293.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Choriocarcinoma / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins*
  • Gene Expression Regulation, Developmental*
  • Humans
  • Interferon Type I / genetics*
  • Interferon Type I / metabolism
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases / metabolism
  • Pregnancy Proteins / genetics*
  • Pregnancy Proteins / metabolism
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins*
  • Trans-Activators / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors*
  • Transcription, Genetic*
  • Transcriptional Activation

Substances

  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • ERF protein, human
  • ETS2 protein, human
  • Interferon Type I
  • Pregnancy Proteins
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factor AP-1
  • Transcription Factors
  • interferon tau
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases