Transcription factor SF1 interacts with AP1, CREB, and TFIIB to regulate basal and cAMP-Stimulated expression of the CYP11A1 gene

Bon Chu Chung

Research output: Contribution to journalArticlepeer-review

Abstract

The cholesterol side-chain cleavage enzyme, which catalyzes the first and rate-limiting step in steroid synthesis, is encoded by the CYP11A1 gene. This gene is expressed mainly in the adrenal and gonad, in response to stimulation by ACTH or gonadotropin. Transcription factor SF1 regulates CYP11A1 and other steroidogenic gene expression through binding to the AAGGTCA sequence. Two SF1-binding sites, located at -50 and -1610 of the human CYPllA1 gene, are required for SF1 function. The binding of SF1 to the -50 site is important for basal expression. A binding assay showed that the hinge region of SF1 interacts directly with the N-terminal region of transcription factor TFIIB. This recruitment of TFIIB could be one important mechanism for SF1 action. The SF1-binding site at -1610 of the gene, flanked by sequences resembling cAMP-responsive elements and AP1-binding sites, is required for cAMP-stimulated transcription. Electrophoretic mobility shift assay demonstrated the binding of SF1, CREB and AP1 to this site. Blocking AP1 function by a dominant negative mutant abolished cAMP response in a dose-dependent fashion, indicating the functional participation of AP1. Many AP1 family members, including c-Jun, JunB, JunD, and c-Fos are present in adrenal Y1 cells, c-Jun and c-Fos, but not JunD, JunB, or FosB, synergistically activates reporter gene expression together with SF1. It indicates that SF1 functionally interacts with selective members of the AP1 family. The interaction of SF1 with AP1 is important for cAMP-stimulated transcription of the CYP11A1, and possibly other steroidogenic genes.

Original languageEnglish
Pages (from-to)A1074
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - Dec 1 1997

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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