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.
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.
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7421, USA. gandrews@kumc.edu
G K
GK
Andrews
D K
DK
Lee
R
R
Ravindra
P
P
Lichtlen
M
M
Sirito
M
M
Sawadogo
W
W
Schaffner
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004032:Diet; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000235:genetics; D004707:Endoderm / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005838:Genotype; D006651:Histocytochemistry; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051720:Upstream Stimulatory Factors; D015017:Yolk Sac / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology*; D000097809:Transcription Factor MTF-1
D000469:Alkaline Phosphatase; D004268:DNA-Binding Proteins; D008668:Metallothionein; D012333:RNA, Messenger; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C497183:Usf1 protein, mouse