Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice

Margaret M. Hinshelwood, Carole R. Mendelson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues, including gonads, placenta, adipose tissue, skin and brain. The 5′-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start of translation in exon II. In ovary, the 5′-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II, while in adipose, the 5′-UTR of CYP19 transcripts is encoded by exon I.4, which lies >20kb upstream of exon II. To map genomic sequences required for ovary- and adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43bp of DNA flanking the 5′-end of ovary-specific exon IIa, or 348bp of 5′- flanking DNA and 170bp of adipose-specific exon I.4 were linked to the human growth hormone (hGH) gene, as reporter, and introduced into transgenic mice. We observed that CYP19(IIa):hGH fusion genes containing as little as 278bp of exon IIa 5′-flanking sequence were expressed at high levels in an ovary-specific manner in transgenic mice, while the CYP19(IIa)-43:hGH fusion gene was not expressed in any tissue. These results suggest that sequences between -43 and -278bp upstream of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the CYP19(I.4)-348:hGH fusion gene, transgene expression was detected in skin and in mammary adipose, but not in any of the other tissues examined. These results indicate that genomic elements within -348 and + 170bp of adipose-specific exon I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in progress using transgenic mice to further define the response elements that mediate ovary and adipose-specific hCYP19 gene expression.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume79
Issue number1-5
DOIs
StatePublished - 2001

Fingerprint

Aromatase
Transgenic Mice
Adipose Tissue
Ovary
Exons
Genes
Tissue
Human Growth Hormone
Gene expression
5' Untranslated Regions
Gene Fusion
Gene Expression
Fusion reactions
Skin
5' Flanking Region
DNA
Gonads
Response Elements
Transgenes
Reporter Genes

Keywords

  • Aromatase
  • Regulation of transcription
  • Tissue-specific expression

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

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title = "Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice",
abstract = "In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues, including gonads, placenta, adipose tissue, skin and brain. The 5′-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start of translation in exon II. In ovary, the 5′-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II, while in adipose, the 5′-UTR of CYP19 transcripts is encoded by exon I.4, which lies >20kb upstream of exon II. To map genomic sequences required for ovary- and adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43bp of DNA flanking the 5′-end of ovary-specific exon IIa, or 348bp of 5′- flanking DNA and 170bp of adipose-specific exon I.4 were linked to the human growth hormone (hGH) gene, as reporter, and introduced into transgenic mice. We observed that CYP19(IIa):hGH fusion genes containing as little as 278bp of exon IIa 5′-flanking sequence were expressed at high levels in an ovary-specific manner in transgenic mice, while the CYP19(IIa)-43:hGH fusion gene was not expressed in any tissue. These results suggest that sequences between -43 and -278bp upstream of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the CYP19(I.4)-348:hGH fusion gene, transgene expression was detected in skin and in mammary adipose, but not in any of the other tissues examined. These results indicate that genomic elements within -348 and + 170bp of adipose-specific exon I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in progress using transgenic mice to further define the response elements that mediate ovary and adipose-specific hCYP19 gene expression.",
keywords = "Aromatase, Regulation of transcription, Tissue-specific expression",
author = "Hinshelwood, {Margaret M.} and Mendelson, {Carole R.}",
year = "2001",
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TY - JOUR

T1 - Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice

AU - Hinshelwood, Margaret M.

AU - Mendelson, Carole R.

PY - 2001

Y1 - 2001

N2 - In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues, including gonads, placenta, adipose tissue, skin and brain. The 5′-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start of translation in exon II. In ovary, the 5′-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II, while in adipose, the 5′-UTR of CYP19 transcripts is encoded by exon I.4, which lies >20kb upstream of exon II. To map genomic sequences required for ovary- and adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43bp of DNA flanking the 5′-end of ovary-specific exon IIa, or 348bp of 5′- flanking DNA and 170bp of adipose-specific exon I.4 were linked to the human growth hormone (hGH) gene, as reporter, and introduced into transgenic mice. We observed that CYP19(IIa):hGH fusion genes containing as little as 278bp of exon IIa 5′-flanking sequence were expressed at high levels in an ovary-specific manner in transgenic mice, while the CYP19(IIa)-43:hGH fusion gene was not expressed in any tissue. These results suggest that sequences between -43 and -278bp upstream of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the CYP19(I.4)-348:hGH fusion gene, transgene expression was detected in skin and in mammary adipose, but not in any of the other tissues examined. These results indicate that genomic elements within -348 and + 170bp of adipose-specific exon I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in progress using transgenic mice to further define the response elements that mediate ovary and adipose-specific hCYP19 gene expression.

AB - In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues, including gonads, placenta, adipose tissue, skin and brain. The 5′-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start of translation in exon II. In ovary, the 5′-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II, while in adipose, the 5′-UTR of CYP19 transcripts is encoded by exon I.4, which lies >20kb upstream of exon II. To map genomic sequences required for ovary- and adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43bp of DNA flanking the 5′-end of ovary-specific exon IIa, or 348bp of 5′- flanking DNA and 170bp of adipose-specific exon I.4 were linked to the human growth hormone (hGH) gene, as reporter, and introduced into transgenic mice. We observed that CYP19(IIa):hGH fusion genes containing as little as 278bp of exon IIa 5′-flanking sequence were expressed at high levels in an ovary-specific manner in transgenic mice, while the CYP19(IIa)-43:hGH fusion gene was not expressed in any tissue. These results suggest that sequences between -43 and -278bp upstream of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the CYP19(I.4)-348:hGH fusion gene, transgene expression was detected in skin and in mammary adipose, but not in any of the other tissues examined. These results indicate that genomic elements within -348 and + 170bp of adipose-specific exon I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in progress using transgenic mice to further define the response elements that mediate ovary and adipose-specific hCYP19 gene expression.

KW - Aromatase

KW - Regulation of transcription

KW - Tissue-specific expression

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