Characterization of the upstream sequence of the human CYP11A1 gene for cell type-specific expression

Shen Ju Chou, Kun Nan Lai, Bon Chu Chung

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme P450scc, which catalyzes the synthesis of steroids from cholesterol. This gene is expressed only in steroidogenic organs such as the adrenal, gonad, placenta, and brain. We have characterized an upstream regulatory element of the human CYP11A1 gene, termed AdE, which contributed to its cell type- specific expression. The AdE sequence contains two protein binding regions, AdE1 and AdE2, which bind many proteins including NF1- and Sp1-like proteins as shown by electrophoretic mobility shift assay, footprinting, competition, antibody supershift, and mutagenesis of the binding sites. When cloned in front of the CYP11A1 promoter or the heterologous thymidine kinase promoter, AdE sequences enhanced expression of the reporter gene in steroidogenic cell lines of the adrenal, gonad, and placental origin but not in nonsteroidogenic cell lines such as COS-1 and Rat-1. The function of AdE1 and AdE2 was lower when present individually than together. The combined action of multiple transcription factors binding to the AdE sequence brings about the final activation of the CYP11A1 gene in a tissue-specific manner.

Original languageEnglish
Pages (from-to)22125-22129
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number36
DOIs
Publication statusPublished - Sep 25 1996

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Cholesterol Side-Chain Cleavage Enzyme
Genes
Gonads
Neurofibromin 1
Cells
Cell Line
Electrophoretic mobility
Mutagenesis
Thymidine Kinase
Electrophoretic Mobility Shift Assay
Reporter Genes
Protein Binding
Placenta
Transcriptional Activation
Rats
Assays
Brain
Proteins
Transcription Factors
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Characterization of the upstream sequence of the human CYP11A1 gene for cell type-specific expression. / Chou, Shen Ju; Lai, Kun Nan; Chung, Bon Chu.

In: Journal of Biological Chemistry, Vol. 271, No. 36, 25.09.1996, p. 22125-22129.

Research output: Contribution to journalArticle

Chou, Shen Ju ; Lai, Kun Nan ; Chung, Bon Chu. / Characterization of the upstream sequence of the human CYP11A1 gene for cell type-specific expression. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 36. pp. 22125-22129.
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