Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains Mihai D. Niculescu, Corneliu N. Craciunescu and Steven H. Zeisel 1 Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina, USA 1 Correspondence: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina, 27599-7461 USA. E-mail: steven_zeisel@unc.edu The availability of choline during critical periods of fetal development alters hippocampal development and affects memory function throughout life. Choline deficiency during fetal development reduces proliferation and migration of neuronal precursor cells in the mouse fetal hippocampus and these changes are associated with modifications in the protein levels of some cell cycle regulators and early differentiation markers. We fed C57 BL/6 mouse dams diets deficient or normal in choline content from days 12 to 17 of pregnancy, and then collected fetal brains on embryonic day 17. Using laser-capture micro-dissection we harvested cells from the ventricular and subventricular zones of Ammon’s horn and from the prime germinal zone of the dentate gyrus (hippocampus). In the ventricular and subventricular zones from the choline-deficient group, we observed increased protein levels for kinase-associated phosphatase (Kap) and for p15 INK4b (two cell cycle inhibitors). In the dentate gyrus, we observed increased levels of calretinin (an early marker of neuronal differentiation). In fetal brain from mothers fed a choline-deficient diet, DNA global methylation was decreased in the ventricular and subventricular zones of Ammon’s horn. We also observed decreased gene-specific DNA methylation of the gene ( Cdkn3 ) that encodes for Kap, correlating with increased expression of this protein. This was not the case for p15 INK4b or calretinin ( Cdkn2b and Calb2 , respectively). These data suggest that choline deficiency-induced changes in gene methylation could mediate the expression of a cell cycle regulator and thereby alter brain development. Key Words: Cdkn3 • Kap • Cdkn2b • p15 INK4b • Calb2 • calretinin • fetal brain • DNA methylation • choline deficiency • hippocampus
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Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains
Niculescu, Mihai D.; Craciunescu, Corneliu N.; Zeisel, Steven H.
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, Volume 20 (1): 43
Fed of American Socs for Experimental Biology – Jan 1, 2006
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