Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase

A. R. Mouw, D. A. Rice, J. C. Meade, Streamson C. Chua, Jr., P. C. White, B. P. Schimmer, K. L. Parker

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The mouse gene encoding adrenal steroid 11β-hydroxylase (11β-OHase) has been cloned and the nucleotide sequence of its 5' end has been determined. The coding regions sequenced are homologous (75%) to the sequence of bovine 11β-OHase cDNA. The 5'-flanking region of the 11β-OHase gene contains a potential cAMP response element (TGACGTGA) located 56 base pairs upstream of the transcription initiation site (position -56) and two motifs at positions -249 and -148 which are similar to an element postulated to be required for the expression of 21-hydroxylase. Transfection of mouse Y1 adrenocortical tumor cells and MA-10 testicular Leydig cells with plasmids containing the 11β-OHase promoter linked to a growth hormone reporter gene showed that the 11β-OHase promoter can direct cell-specific expression. Deletion analyses of the 5'-flanking region suggest that multiple sequence elements, one of which is located between positions -425 and -338 and a second between positions -338 and -123, interact to produce full levels of promoter activity. Mutant Y1 cells defective in cAMP-dependent protein kinase activity do not express growth hormone driven by the 11β-OHase promoter, indicating that expression of 11β-OHase in Y1 cells requires an intact cAMP second messenger system. Moreover, mutation of the putative cAMP response element at position -56 abolishes expression. These experiments thus present a useful system for the investigation of cis-acting elements involved in the transcriptional regulation of 11β-OHase.

Original languageEnglish (US)
Pages (from-to)1305-1309
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number2
StatePublished - 1989
Externally publishedYes

Fingerprint

Steroid 11-beta-Hydroxylase
Functional analysis
Gene encoding
5' Flanking Region
Response Elements
Genetic Promoter Regions
Structural analysis
Growth Hormone
Genes
Steroid 21-Hydroxylase
Transcription Initiation Site
Second Messenger Systems
Cyclic AMP-Dependent Protein Kinases
Tumors
Plasmids
Nucleotides
Complementary DNA
Cells
Leydig Cells
Reporter Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mouw, A. R., Rice, D. A., Meade, J. C., Chua, Jr., S. C., White, P. C., Schimmer, B. P., & Parker, K. L. (1989). Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase. Journal of Biological Chemistry, 264(2), 1305-1309.

Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase. / Mouw, A. R.; Rice, D. A.; Meade, J. C.; Chua, Jr., Streamson C.; White, P. C.; Schimmer, B. P.; Parker, K. L.

In: Journal of Biological Chemistry, Vol. 264, No. 2, 1989, p. 1305-1309.

Research output: Contribution to journalArticle

Mouw, AR, Rice, DA, Meade, JC, Chua, Jr., SC, White, PC, Schimmer, BP & Parker, KL 1989, 'Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase', Journal of Biological Chemistry, vol. 264, no. 2, pp. 1305-1309.
Mouw, A. R. ; Rice, D. A. ; Meade, J. C. ; Chua, Jr., Streamson C. ; White, P. C. ; Schimmer, B. P. ; Parker, K. L. / Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase. In: Journal of Biological Chemistry. 1989 ; Vol. 264, No. 2. pp. 1305-1309.
@article{0e23e78c9a37458f8ab1ace4f9ef6b71,
title = "Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase",
abstract = "The mouse gene encoding adrenal steroid 11β-hydroxylase (11β-OHase) has been cloned and the nucleotide sequence of its 5' end has been determined. The coding regions sequenced are homologous (75{\%}) to the sequence of bovine 11β-OHase cDNA. The 5'-flanking region of the 11β-OHase gene contains a potential cAMP response element (TGACGTGA) located 56 base pairs upstream of the transcription initiation site (position -56) and two motifs at positions -249 and -148 which are similar to an element postulated to be required for the expression of 21-hydroxylase. Transfection of mouse Y1 adrenocortical tumor cells and MA-10 testicular Leydig cells with plasmids containing the 11β-OHase promoter linked to a growth hormone reporter gene showed that the 11β-OHase promoter can direct cell-specific expression. Deletion analyses of the 5'-flanking region suggest that multiple sequence elements, one of which is located between positions -425 and -338 and a second between positions -338 and -123, interact to produce full levels of promoter activity. Mutant Y1 cells defective in cAMP-dependent protein kinase activity do not express growth hormone driven by the 11β-OHase promoter, indicating that expression of 11β-OHase in Y1 cells requires an intact cAMP second messenger system. Moreover, mutation of the putative cAMP response element at position -56 abolishes expression. These experiments thus present a useful system for the investigation of cis-acting elements involved in the transcriptional regulation of 11β-OHase.",
author = "Mouw, {A. R.} and Rice, {D. A.} and Meade, {J. C.} and {Chua, Jr.}, {Streamson C.} and White, {P. C.} and Schimmer, {B. P.} and Parker, {K. L.}",
year = "1989",
language = "English (US)",
volume = "264",
pages = "1305--1309",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "2",

}

TY - JOUR

T1 - Structural and functional analysis of the promoter region of the gene encoding mouse steroid 11β-hydroxylase

AU - Mouw, A. R.

AU - Rice, D. A.

AU - Meade, J. C.

AU - Chua, Jr., Streamson C.

AU - White, P. C.

AU - Schimmer, B. P.

AU - Parker, K. L.

PY - 1989

Y1 - 1989

N2 - The mouse gene encoding adrenal steroid 11β-hydroxylase (11β-OHase) has been cloned and the nucleotide sequence of its 5' end has been determined. The coding regions sequenced are homologous (75%) to the sequence of bovine 11β-OHase cDNA. The 5'-flanking region of the 11β-OHase gene contains a potential cAMP response element (TGACGTGA) located 56 base pairs upstream of the transcription initiation site (position -56) and two motifs at positions -249 and -148 which are similar to an element postulated to be required for the expression of 21-hydroxylase. Transfection of mouse Y1 adrenocortical tumor cells and MA-10 testicular Leydig cells with plasmids containing the 11β-OHase promoter linked to a growth hormone reporter gene showed that the 11β-OHase promoter can direct cell-specific expression. Deletion analyses of the 5'-flanking region suggest that multiple sequence elements, one of which is located between positions -425 and -338 and a second between positions -338 and -123, interact to produce full levels of promoter activity. Mutant Y1 cells defective in cAMP-dependent protein kinase activity do not express growth hormone driven by the 11β-OHase promoter, indicating that expression of 11β-OHase in Y1 cells requires an intact cAMP second messenger system. Moreover, mutation of the putative cAMP response element at position -56 abolishes expression. These experiments thus present a useful system for the investigation of cis-acting elements involved in the transcriptional regulation of 11β-OHase.

AB - The mouse gene encoding adrenal steroid 11β-hydroxylase (11β-OHase) has been cloned and the nucleotide sequence of its 5' end has been determined. The coding regions sequenced are homologous (75%) to the sequence of bovine 11β-OHase cDNA. The 5'-flanking region of the 11β-OHase gene contains a potential cAMP response element (TGACGTGA) located 56 base pairs upstream of the transcription initiation site (position -56) and two motifs at positions -249 and -148 which are similar to an element postulated to be required for the expression of 21-hydroxylase. Transfection of mouse Y1 adrenocortical tumor cells and MA-10 testicular Leydig cells with plasmids containing the 11β-OHase promoter linked to a growth hormone reporter gene showed that the 11β-OHase promoter can direct cell-specific expression. Deletion analyses of the 5'-flanking region suggest that multiple sequence elements, one of which is located between positions -425 and -338 and a second between positions -338 and -123, interact to produce full levels of promoter activity. Mutant Y1 cells defective in cAMP-dependent protein kinase activity do not express growth hormone driven by the 11β-OHase promoter, indicating that expression of 11β-OHase in Y1 cells requires an intact cAMP second messenger system. Moreover, mutation of the putative cAMP response element at position -56 abolishes expression. These experiments thus present a useful system for the investigation of cis-acting elements involved in the transcriptional regulation of 11β-OHase.

UR - http://www.scopus.com/inward/record.url?scp=0024557788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024557788&partnerID=8YFLogxK

M3 - Article

C2 - 2783417

AN - SCOPUS:0024557788

VL - 264

SP - 1305

EP - 1309

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 2

ER -