Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3436-3444
Differential Regulation of Coproporphyrinogen Oxidase Gene Between
Erythroid and Nonerythroid Cells
Shinichiro Takahashi,
Shigeru Taketani,
Jun-etsu Akasaka,
Akira Kobayashi,
Norio Hayashi,
Masayuki Yamamoto, and
Tadashi Nagai
From the Department of Biochemistry, Tohoku University School of
Medicine, Sendai, Japan; Department of Hygiene, Kansai Medical
University, Moriguchi, Japan; and the Center for Tsukuba Advanced
Research Alliance, (TARA) and Institute of Basic Medical Sciences,
University of Tsukuba, Tsukuba, Japan.
Coproporphyrinogen oxidase (CPO) catalyzes the sixth step of the
heme biosynthetic pathway. To assess the tissue-specific regulation of
the CPO gene promoter, mouse genomic DNA clones for CPO were isolated.
Structural analysis demonstrated that the mouse CPO gene spans
approximately 11 kb and consists of seven exons, just like its human
counterpart. Functional analysis of the promoter by transient
transfection assays indicated that synergistic action between an
SP-1-like element at
21/
12, a GATA site at
59/
54, and a
novel regulatory element, CPRE (-GGACTACAG-) at
49/
41, is
essential for the promoter activity in murine
erythroleukemia (MEL) cells. In nonerythroid NIH3T3 cells, however, the
GATA site is not required. Gel mobility shift assays demonstrated that
specific DNA-protein complexes can be formed with each element, and
that there are cell-specific differences in factors, which bind to the
SP-1-like element between MEL and NIH3T3 cells. These results provide
evidence for differential regulation of the promoter function of CPO
gene between erythroid and nonerythroid cells.
© 1998 by The American Society of Hematology.