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| Status |
Public on Sep 13, 2013 |
| Title |
Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites [methylation array] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG island–containing promoters but enriched in predicted enhancers. Classification of the DM sites into those undermethylated in neurons (neuronal type) and those undermethylated in nonneuronal cells (glial type), combined with findings of others that methylation within control elements typically negatively correlates with gene expression, yielded large sets of predicted neuron-specific and non– neuron-specific genes. These sets of predicted genes were in excellent agreement with the available direct measurements of gene expression in human and mouse. We also found a distinct set of DNA methylation patterns that were unique for neuronal cells. In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors. Finally, non-CpG methylation was substantially more prevalent in neurons than in nonneuronal cells.
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| Overall design |
Genomic DNA was isolated from FACS-sorted human brain neuronal and nonneuronal nuclei. DNA was bisulfite converted and hybridised to the Illumina Infinium 450K Human Methylation Beadchip array. Six subjects in two technical replicate expriments were analyzed.
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| Contributor(s) |
Kozlenkov A, Dracheva S |
| Citation |
Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites; Alexey Kozlenkov, Panos Roussos, Alisa Timashpolsky, Mihaela Barbu, Sergei Rudchenko, Marina Bibikova, Brandy Klotzle, William Byne, Rebecca Lyddon, Antonio Fabio Di Narzo, Yasmin L. Hurd, Eugene V. Koonin and Stella Dracheva; Accepted for publication in Nucleic Acids Research (28-Aug-2013)
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| Submission date |
Sep 11, 2013 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Stella Dracheva |
| E-mail(s) |
stella.dracheva@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Dept. of Psychiatry
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| Street address |
James J. Peters VA Medical Center,130 W Kingsbridge Rd
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| City |
Bronx |
| State/province |
New York |
| ZIP/Postal code |
10468 |
| Country |
USA |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE50853 |
Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites |
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| Relations |
| BioProject |
PRJNA219103 |
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