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Volume 270,
Number 42,
Issue of October 20, 1995 pp. 25064-25069
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Regulation
of Placenta-specific Expression of the Aromatase Cytochrome P-450 Gene
INVOLVEMENT OF THE TROPHOBLAST-SPECIFIC ELEMENT BINDING PROTEIN
(Received for publication, July 24, 1995; and in revised form, August 8, 1995)
Kazuyo
Yamada ,
Nobuhiro
Harada ,
Shin-ichiro
Honda,
Yasuyuki
Takagi
The aromatase (cytochrome P-450 ) gene contains
multiple untranslated exons I that are differentially transcribed in a
tissue-specific manner. DNA sequences within the initial -301
upstream of placenta-specific exon I (exon Ia) are sufficient for
placenta-specific expression of aromatase. In gel mobility shift assay,
three separate domains in this region form specific binding complexes
with proteins extracted from choriocarcinoma JEG-3 nuclei. A fragment
containing these domains activates transcription driven by a
heterologous promoter in a cell type-specific manner. Two of the
binding domains that form major complexes in gel shift assay compete
with each other and with a DNA fragment containing the
trophoblast-specific element (TSE), which is derived from the enhancer
region of the human chorionic gonadotropin -subunit gene and is
believed to confer placenta-specific expression of the gene. The core
sequence RNCCTNNRG is sufficient for recognition of the TSE-binding
protein, which is detected only in nuclear extracts prepared from
placenta and choriocarcinoma. A mutation introduced in the distal TSE
core in aromatase promoter resulted in marked reduction of
transcriptional activity, although TSE region by itself did not show
enhancer activity as that in human chorionic gonadotropin -subunit
gene.

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Copyright © 1995 by the American Society for Biochemistry and Molecular Biology.
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