Regulation of rat steroid 11β-hydroxylase gene: Suppression of transcriptional activation involving AP-1 factors through an upstream element

Kuniaki Mukai, Masataka Nagakane, Fumiko Mitani, Yuzuru Ishimura

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Abstract

Steroid 11β-hydroxylase gene (CYP11B1) encodes a cytochrome P450 catalyzing the last steps for the synthesis of cortisol and corticosterone in humans and rodents, respectively. The gene is expressed in the zonae fasciculata-reticularis of adrenal cortices. Our previous studies have shown that transcription of rat CYP11B1 is activated by binding of AP-1 transcription factor complexes to their site in the 5′-flanking region of the gene. AP-1 factors have been found to be involved in zone-specific transcription as well as adrenocorticotropic hormone (ACTH)-inducible transcription. AP-1 factors, however, are expressed in cells of various tissues, suggesting a mechanism suppressing the activation by AP-1 in cells that express AP-1 factors, but not CYP11B1. In this study, we analyzed a mechanism of transcriptional repression utilizing NIH3T3 cells as those express AP-1 factors, but not CYP11B1. Transient transfection assays with NIH3T3 cells using the 5′-region of CYP11B1 up to −8.7 kb from the transcriptional initiation site revealed that the 0.15-kb region from −0.65 to −0.5 kb had a strong repressive effect on the proximal 0.5-kb promoter activity involving AP-1 factors. On the other hand, the 0.15-kb region did not show any regulatory effect on the 0.5-kb promoter activity in Y-1 adrenocortical cells that express both CYP11B1 and AP-1 factors. Nuclear protein extracts from NIH3T3, but not Y-1 cells, contained DNA-binding activity for the 0.15-kb sequence, suggesting that the nuclear protein plays a role in the suppression of transcriptional activation involving AP-1 factors.

Original languageEnglish
Pages (from-to)171-176
Number of pages6
JournalInternational Congress Series
Volume1233
Issue numberC
DOIs
Publication statusPublished - 2002 Nov 1

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Keywords

  • Adrenal cortex
  • AP-1
  • Steroid 11β-hydroxylase
  • Steroidogenesis
  • Transcription

ASJC Scopus subject areas

  • Medicine(all)

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