Article

Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons.

Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Genome Research (impact factor: 13.61). 04/2011; 21(5):688-96. DOI:10.1101/gr.112755.110 pp.688-96
Source: PubMed

ABSTRACT Epigenome information in mammalian brain cells reflects their developmental history, neuronal activity, and environmental exposures. Studying the epigenetic modifications present in neuronal cells is critical to a more complete understanding of the role of the genome in brain functions. We performed comprehensive DNA methylation analysis in neuronal and non-neuronal nuclei obtained from the human prefrontal cortex. Neuronal nuclei manifest qualitatively and quantitatively distinctive DNA methylation patterns, including relative global hypomethylation, differential enrichment of transcription-factor binding sites, and higher methylation of genes expressed in astrocytes. Non-neuronal nuclei showed indistinguishable DNA methylation patterns from bulk cortex and higher methylation of synaptic transmission-related genes compared with neuronal nuclei. We also found higher variation in DNA methylation in neuronal nuclei, suggesting that neuronal cells have more potential ability to change their epigenetic status in response to developmental and environmental conditions compared with non-neuronal cells in the central nervous system.

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    Article: Diametrically opposite methylome-transcriptome relationships in high- and low-CpG promoter genes in postmitotic neural rat tissue.
    Theresa Hartung, Lu Zhang, Rahul Kanwar, Irina Khrebtukova, Matthias Reinhardt, Cheng Wang, Terry M Therneau, Michaela S Banck, Gary P Schroth, Andreas S Beutler
    [show abstract] [hide abstract]
    ABSTRACT: DNA methylation can control some CpG-poor genes but unbiased studies have not found a consistent genome-wide association with gene activity outside of CpG islands or shores possibly due to use of cell lines or limited bioinformatics analyses. We performed reduced representation bisulfite sequencing (RRBS) of rat dorsal root ganglia encompassing postmitotic primary sensory neurons (n = 5, r > 0.99; orthogonal validation p < 10(-19)). The rat genome suggested a dichotomy of genes previously reported in other mammals: low CpG content (< 3.2%) promoter (LCP) genes and high CpG content (≥ 3.2%) promoter (HCP) genes. A genome-wide integrated methylome-transcriptome analysis showed that LCP genes were markedly hypermethylated when repressed, and hypomethylated when active with a 40% difference in a broad region at the 5' of the transcription start site (p < 10(-87) for -6000 bp to -2000 bp, p < 10(-73) for -2000 bp to +2000 bp, no difference in gene body p = 0.42). HCP genes had minimal TSS-associated methylation regardless of transcription status, but gene body methylation appeared to be lost in repressed HCP genes. Therefore, diametrically opposite methylome-transcriptome associations characterize LCP and HCP genes in postmitotic neural tissue in vivo.
    Epigenetics: official journal of the DNA Methylation Society 05/2012; 7(5):421-8. · 4.58 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

central nervous system
 
complete understanding
 
differential enrichment
 
epigenetic modifications present
 
epigenetic status
 
human prefrontal cortex
 
neuronal
 
neuronal activity
 
neuronal cells
 
neuronal nuclei
 
Neuronal nuclei manifest qualitatively
 
non-neuronal cells
 
Non-neuronal nuclei
 
potential ability
 
quantitatively distinctive DNA methylation patterns
 
relative global hypomethylation
 
transcription-factor binding sites
 

Kazuya Iwamoto