Dysregulation of Neuronal Genes by Fetal-Neonatal Iron Deficiency Anemia Is Associated with Altered DNA Methylation in the Rat Hippocampus.
DNA methylation
DNA sequencing
hippocampus
iron
micronutrient deficiency
neurobiology
neuroplasticity
transcriptome
Journal
Nutrients
ISSN: 2072-6643
Titre abrégé: Nutrients
Pays: Switzerland
ID NLM: 101521595
Informations de publication
Date de publication:
27 May 2019
27 May 2019
Historique:
received:
17
04
2019
revised:
21
05
2019
accepted:
22
05
2019
entrez:
30
5
2019
pubmed:
30
5
2019
medline:
31
12
2019
Statut:
epublish
Résumé
Early-life iron deficiency results in long-term abnormalities in cognitive function and affective behavior in adulthood. In preclinical models, these effects have been associated with long-term dysregulation of key neuronal genes. While limited evidence suggests histone methylation as an epigenetic mechanism underlying gene dysregulation, the role of DNA methylation remains unknown. To determine whether DNA methylation is a potential mechanism by which early-life iron deficiency induces gene dysregulation, we performed whole genome bisulfite sequencing to identify loci with altered DNA methylation in the postnatal day (P) 15 iron-deficient (ID) rat hippocampus, a time point at which the highest level of hippocampal iron deficiency is concurrent with peak iron demand for axonal and dendritic growth. We identified 229 differentially methylated loci and they were mapped within 108 genes. Among them, 63 and 45 genes showed significantly increased and decreased DNA methylation in the P15 ID hippocampus, respectively. To establish a correlation between differentially methylated loci and gene dysregulation, the methylome data were compared to our published P15 hippocampal transcriptome. Both datasets showed alteration of similar functional networks regulating nervous system development and cell-to-cell signaling that are critical for learning and behavior. Collectively, the present findings support a role for DNA methylation in neural gene dysregulation following early-life iron deficiency.
Identifiants
pubmed: 31137889
pii: nu11051191
doi: 10.3390/nu11051191
pmc: PMC6566599
pii:
doi:
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS099178
Pays : United States
Organisme : NINDS NIH HHS
ID : R01NS099178
Pays : United States
Organisme : National Institute of Child Health and Human Development
ID : R01 HD29421-20
Déclaration de conflit d'intérêts
Y.-C. Lien, D.E. Condon, M.K. Georgieff, R.A. Simmons, and P.V. Tran have no conflict of interest.
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