Actions of two different cAMP-responsive sequences and an enhancer of the human CYP11A1 (P450scc) gene in adrenal Y1 and placental JEG-3 cells

Ing Cherng Guo, Huei Man Tsai, Bon Chu Chung

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

We have characterized three cis-acting elements of the human CYP11A1 gene. A proximal cAMP-responsive sequence (P-CRS) functioned in both adrenal Y1 and placental JEG-3 cells. An upstream cAMP-responsive sequence (U-CRS) and an enhancer, localized by transfections of deleted gene segments linked to a reporter gene to bases -1621 to -1503 and -1931 to -1822, respectively, functioned in Y1 but not JEG-3 cells. Both regions bind proteins only from Y1 cells as identified by footprinting analysis. U-CRS contains the TCAAGGTCA sequence that binds the nuclear receptor family of proteins. The cAMP- dependent transcription mediated by U-CRS, but not by P-CRS, was abolished in a cell line deficient in cAMP-dependent protein kinase. Therefore, P-CRS and U-CRS use different effectors to mediate cAMP response. Gel mobility shift, competition, and antibody supershift experiments showed that nucleotides - 117 to -94, which contributed to P-CRS activity in transfection experiments, bound weakly to Sp1-like proteins. This feature is shared by many proximal regulatory elements of steroidogenic genes. Therefore, steroidogenic genes could be coordinately regulated through common regulatory elements such as P- CRS, U-CRS, and cell type-selective enhancers.

Original languageEnglish
Pages (from-to)6362-6369
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number9
Publication statusPublished - Mar 4 1994

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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