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Estrogen induces the PEMT (phosphatidylethanolamine N‐methyltransferase) gene in human and murine hepatocytes
Author(s) -
Resseguie Mary E,
Niculescu Mihai,
Costa KerryAnn da,
Randall Thomas,
Zeisel Steven
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a61-d
Subject(s) - estrogen , promoter , enhancer , biology , gene , transcription factor , gene expression , regulation of gene expression , methyltransferase , endocrinology , medicine , genetics , methylation
Choline is an essential nutrient for humans, though some part of this requirement can be met by endogenous synthesis catalyzed by phosphatidylethanolamine N ‐methyltransferase ( PEMT ). Pre‐menopausal women are relatively resistant to dietary choline deficiency compared to post‐menopausal women and men, suggesting that estrogen may increase PEMT activity. The aim of this study is to investigate whether PEMT gene expression is regulated by estrogen. RT‐PCR revealed gene transcription was increased in a dose‐dependent manner in cultured primary mouse and human hepatocytes treated with various concentrations of 17B‐estradiol. In both mouse and human hepatocytes, this increased message preceded an increase in protein expression and enzyme activity. Using bioinformatics approaches, we found that the murine and human PEMT promoters share three evolutionarily conserved regions which contain putative estrogen regulatory motifs: estrogen response elements (ERE), AP‐1 and FoxA‐1 sites. In addition, we report a region in the human gene containing a consensus ERE, and core promoter elements, located upstream of the putative promoter, which may function as an alternative promoter and/or an enhancer region. This study is the first to explore the underlying mechanism of why premenopausal women are resistant to dietary choline deficiency. This work supported by NIH grants to SZ (DK55865, AG09525, DK56350).