Journal
FASEB JOURNAL
Volume 21, Issue 10, Pages 2622-2632Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.07-8227com
Keywords
choline; 17-beta-estradiol; bioinformatics; ERE; evolutionarily conserved gene motifs
Categories
Funding
- NIA NIH HHS [P01 AG009525, P01 AG009525-160005, AG09525] Funding Source: Medline
- NIDDK NIH HHS [P30 DK056350, DK56350, DK55865, P30 DK056350-08, R01 DK055865-07, R01 DK055865] Funding Source: Medline
- NIEHS NIH HHS [P30 ES010126, ES10126, P30 ES010126-089008] Funding Source: Medline
Ask authors/readers for more resources
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) similar to 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available