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EMBO J. 2001 Mar 1;20 (5):1114-22
11230134 [Cited:
9]
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The transcription factors MTF-1 and USF1 cooperate
to regulate mouse metallothionein-I expression in response to the
essential metal zinc in visceral endoderm cells during early
development.
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[My paper]
G K
Andrews
,
D K Lee
,
R
Ravindra
,
P
Lichtlen
,
M
Sirito
,
M
Sawadogo
,
W
Schaffner
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During early development of the mouse embryo,
expression of the metallothionein-I (MT-I) gene is heightened
specifically in the endoderm cells of the visceral yolk sac. The
mechanisms of regulation of this cell-specific pattern of
expression of metallothionein-I are unknown. However, it has
recently been shown that MTF-1, functioning as a metalloregulatory
transcription factor, activates metallothionein genes in response
to the essential metal zinc. In contrast with the metallothionein
genes, MTF-1 is essential for development; null mutant embryos die
due to liver degeneration. We report here that MTF-1 is absolutely
essential for upregulation of MT-I gene expression in visceral
endoderm cells and that optimal expression also involves
interactions of the basic helix-loop-helix upstream stimulatory
factor-1 (USF1) with an E-box1-containing sequence at -223 bp in
the MT-I promoter. Expression of MT-I in visceral endoderm cells
was dependent on maternal dietary zinc. Thus, the essential metal,
zinc, apparently provides the signaling ligand that activates
cell-specific MT-I expression in visceral endoderm
cells.
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| Mesh-terms:
Alkaline Phosphatase,
genetics;
Animals;
DNA-Binding Proteins,
metabolism;
Diet;
Embryo and Fetal Development,
drug effects;
Embryo and Fetal Development,
genetics;
Endoderm, cytology;
Endoderm, drug
effects;
Endoderm, metabolism;
Female;
Gene Deletion;
Gene Expression Regulation,
Developmental, drug effects;
Genotype;
Histocytochemistry;
Metallothionein,
genetics;
Metallothionein,
metabolism;
Mice;
Mice, Knockout;
Mice, Transgenic;
Pregnancy;
Promoter Regions (Genetics),
genetics;
RNA, Messenger,
genetics;
RNA, Messenger,
metabolism;
Response Elements,
genetics;
Support, U.S. Gov't,
P.H.S.;
Transcription Factors,
genetics;
Transcription Factors,
metabolism;
Yolk Sac, cytology;
Yolk Sac, drug
effects;
Yolk Sac, embryology;
Yolk Sac, metabolism;
Zinc, administration &
dosage;
Zinc, deficiency;
Zinc,
pharmacology;
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Notes by chiroted:
DNA for Metallothionein-I expression with Antidote Zinc Orotate!