Genome-wide divergence of DNA methylation marks in cerebral and cerebellar cortices.
BACKGROUND
Emerging evidence suggests that DNA methylation plays an expansive role in the central nervous system (CNS). Large-scale whole genome DNA methylation profiling of the normal human brain offers tremendous potential in understanding the role of DNA methylation in brain development and function.


RESULTS
Using methylation-sensitive SNP chip analysis (MSNP), we performed whole genome DNA methylation profiling of the prefrontal, occipital, and temporal regions of cerebral cortex, as well as cerebellum. These data provide an unbiased representation of CpG sites comprising 377,509 CpG dinucleotides within both the genic and intergenic euchromatic region of the genome. Our large-scale genome DNA methylation profiling reveals that the prefrontal, occipital, and temporal regions of the cerebral cortex compared to cerebellum have markedly different DNA methylation signatures, with the cerebral cortex being hypermethylated and cerebellum being hypomethylated. Such differences were observed in distinct genomic regions, including genes involved in CNS function. The MSNP data were validated for a subset of these genes, by performing bisulfite cloning and sequencing and confirming that prefrontal, occipital, and temporal cortices are significantly more methylated as compared to the cerebellum.


CONCLUSIONS
These findings are consistent with known developmental differences in nucleosome repeat lengths in cerebral and cerebellar cortices, with cerebrum exhibiting shorter repeat lengths than cerebellum. Our observed differences in DNA methylation profiles in these regions underscores the potential role of DNA methylation in chromatin structure and organization in CNS, reflecting functional specialization within cortical regions.
Xin
Yurong
Y
Department of Psychiatry, Columbia University and The New York State Psychiatric Institute, New York, New York, United States of America.
Chanrion
Benjamin
B
Liu
Meng-Min
MM
Galfalvy
Hanga
H
Costa
Ramiro
R
Ilievski
Boro
B
Rosoklija
Gorazd
G
Arango
Victoria
V
Dwork
Andrew J
AJ
Mann
J John
JJ
Tycko
Benjamin
B
Haghighi
Fatemeh
F
D002540:Cerebral Cortex / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D015894:Genome, Human; D006801:Humans