5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging.
DNA methylation dynamics influence brain function and are altered in neurological disorders. 5-hydroxymethylcytosine (5-hmC), a DNA base that is derived from 5-methylcytosine, accounts for ∼40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity. We mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages, which allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood. We found developmentally programmed acquisition of 5-hmC in neuronal cells. Epigenomic localization of 5-hmC-regulated regions revealed stable and dynamically modified loci during neurodevelopment and aging. By profiling 5-hmC in human cerebellum, we found conserved genomic features of 5-hmC. Finally, we found that 5-hmC levels were inversely correlated with methyl-CpG-binding protein 2 dosage, a protein encoded by a gene in which mutations cause Rett syndrome. These data suggest that 5-hmC-mediated epigenetic modification is critical in neurodevelopment and diseases.
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Keith E
KE
Szulwach
Xuekun
X
Li
Yujing
Y
Li
Chun-Xiao
CX
Song
Hao
H
Wu
Qing
Q
Dai
Hasan
H
Irier
Anup K
AK
Upadhyay
Marla
M
Gearing
Allan I
AI
Levey
Aparna
A
Vasanthakumar
Lucy A
LA
Godley
Qiang
Q
Chang
Xiaodong
X
Cheng
Chuan
C
He
Peng
P
Jin
D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000375:Aging / Q000187:drug effects* / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019175:DNA Methylation; D004195:Disease Models, Animal; D057890:Epigenomics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics
D051783:Methyl-CpG-Binding Protein 2; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D010751:Phosphopyruvate Hydratase