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.
N1 - Funding Information:
The authors thank Dr. Katherine Graves for generation of transgenic mice and Mr. John Shelton for carrying out in situ hybridization. The authors also thank Margaret Smith for performing the northern analyses and Barbara Murry for conducting immunohistochemical analysis. This research was supported by the National Institutes of Health Grant 5 R01 DK31206.
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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U2 - 10.1016/S0960-0760(01)00157-1
DO - 10.1016/S0960-0760(01)00157-1
M3 - Article
C2 - 11850225
AN - SCOPUS:0035714535
SN - 0960-0760
VL - 79
SP - 193
EP - 201
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-5
ER -