Isis Trujillo 1, Natalia Surzenko 1, Yanyan Wang 2 and Steven H Zeisel 1 (2016). DNA Methylation and microRNA Expression are Altered by Choline Deficiency During Mouse Brain Development. The FASEB Journal, 30(1).
1. University of North Carolina at Chapel Hill, Kannapolis, NC
2. Medical Genetics, Third Military Medical University, Chonggin, China, People’s Republic of
Choline is an essential nutrient that is obtained from the diet and through de novo synthesis. During fetal development, the embryo’s source of choline is obtained form its mother. Our group demonstrated in mice that maternal choline deficiency (CD) during embryo development changes the proliferation rates and differentiation patterns of neural progenitor cells (NPC), leading to altered layer architecture in the cerebral cortex. This outcome is due to premature differentiation and depletion of NPCs in the developing brain, and is in part mediated through the downregulation of the epidermal growth factor receptor (EGFR) protein expression in NPCs. In this study we test the hypothesis that epigenetic changes in DNA methylation and histone marks in CD NPCs lead to aberrant expression of miRNAs, causing the phenotypes observed in CD brains. Consistent with the increase in DNA methylation during priming for differentiation, and an increase in differentiating cells in the developing cortex of CD embryos, we found an increase in DNA methylation in CD brains at embryonic day 17 (E17). To extend these findings, we are currently evaluating the expression of histone marks, H3K9me3 and H3K27me3, in CD NPCs. Our preliminary data indicates that expression of multiple microRNAs (miRNAs) is changed in CD NPCs, including miR-129-5p, which targets Egfr and is upregulated in CD brains. Next, we will determine whether aberrant expression of miR-129-5p or other candidate miRNAs in CD E17 brains in vivo, alters NPC proliferative and differentiation properties. This approach will allow us to characterize the molecular mechanisms whereby choline regulates NPC behavior and brain development.