title: Cellular DNA methylation program during neurulation and its alteration by alcohol exposure.
abstract: BACKGROUND
  Epigenetic changes are believed to be among the earliest key regulators for cell fate and embryonic development. To support this premise, it is important to understand whether or not systemic epigenetic changes coordinate with the progression of development. We have demonstrated that DNA methylation is programmed when neural stem cells differentiate (Zhou et al.,2011). Here, we analyzed the DNA methylation events that occur during early neural tube development.
  
  
  RESULTS
  Using immunocytochemistry, we demonstrated that the DNA methylation marks - 5-methylcytosine (5-MeC), DNA methylation binding domain 1 (MBD1), and DNA methytransferases 1 (DNMT1) were highly coordinated in temporal and spatial patterns that paralleled the progress of embryonic development. The above ontogenic program of DNA methylation was, however, subjected to environmental modification. Alcohol exposure during fetal development, which is known to cause fetal alcohol spectrum disorder, altered the density and distribution of the DNA methylation marks. The alcohol exposure (88 mM) over 6 or 44 hours at gestation day 8 (GD-8) to GD-10 altered timely DNA methylation and retarded embryonic growth. We further demonstrated that the direct inhibiting of DNA methylation with 5-aza-cytidine (5-AZA) resulted in similar growth retardation.
  
  
  CONCLUSIONS
  We identified a temporal and spatial cellular DNA methylation program after initial erasure, which parallels embryonic maturation. Alcohol delayed the cellular DNA methylation program and also retarded embryonic growth. Since direct inhibiting of DNA methylation resulted in similar retardation, alcohol thus can affect embryonic development through a epigenetic pathway.
authors.affiliation: Department of Anatomy & Cell Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA. imce100@iupui.edu
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ada
authors.initials: A
authors.lastname: Love
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000378:metabolism; D054259:Neural Tube / Q000187:drug effects / Q000196:embryology; D054261:Neurulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D012097:Repressor Proteins / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C485852:Dmap1 protein, mouse; C066141:MBD1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D000431:Ethanol; D044503:5-Methylcytosine; D001374:Azacitidine