Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes.
Choline is an essential nutrient for humans, though some of the requirement can be met by endogenous synthesis catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). Premenopausal women are relatively resistant to choline deficiency compared with postmenopausal women and men. Studies in animals suggest that estrogen treatment can increase PEMT activity. In this study we investigated whether the PEMT gene is regulated by estrogen. PEMT transcription was increased in a dose-dependent manner when primary mouse and human hepatocytes were treated with 17-beta-estradiol for 24 h. This increased message was associated with an increase in protein expression and enzyme activity. In addition, we report a region that contains a perfect estrogen response element (ERE) approximately 7.5 kb from the transcription start site corresponding to transcript variants NM_007169 and NM-008819 of the human and murine PEMT genes, respectively, three imperfect EREs in evolutionarily conserved regions and multiple imperfect EREs in nonconserved regions in the putative promoter regions. We predict that both the mouse and human PEMT genes have three unique transcription start sites, which are indicative of either multiple promoters and/or alternative splicing. This study is the first to explore the underlying mechanism of why dietary requirements for choline vary with estrogen status in humans.
Resseguie
Mary
M
Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461, USA.
Song
Jiannan
J
Niculescu
Mihai D
MD
da Costa
Kerry-Ann
KA
Randall
Thomas A
TA
Zeisel
Steven H
SH
D017398:Alternative Splicing; D000818:Animals; D002478:Cells, Cultured; D002796:Choline Deficiency / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D008297:Male; D051379:Mice; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000235:genetics*; D017698:Postmenopause; D017697:Premenopause; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D004958:Estradiol; C494489:PEMT protein, human; D050918:Phosphatidylethanolamine N-Methyltransferase