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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 func...

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Autores principales: Xin, Yurong, Chanrion, Benjamin, Liu, Meng-Min, Galfalvy, Hanga, Costa, Ramiro, Ilievski, Boro, Rosoklija, Gorazd, Arango, Victoria, Dwork, Andrew J., Mann, J. John, Tycko, Benjamin, Haghighi, Fatemeh
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893206/
https://www.ncbi.nlm.nih.gov/pubmed/20596539
http://dx.doi.org/10.1371/journal.pone.0011357
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author Xin, Yurong
Chanrion, Benjamin
Liu, Meng-Min
Galfalvy, Hanga
Costa, Ramiro
Ilievski, Boro
Rosoklija, Gorazd
Arango, Victoria
Dwork, Andrew J.
Mann, J. John
Tycko, Benjamin
Haghighi, Fatemeh
author_facet Xin, Yurong
Chanrion, Benjamin
Liu, Meng-Min
Galfalvy, Hanga
Costa, Ramiro
Ilievski, Boro
Rosoklija, Gorazd
Arango, Victoria
Dwork, Andrew J.
Mann, J. John
Tycko, Benjamin
Haghighi, Fatemeh
author_sort Xin, Yurong
collection PubMed
description 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. METHODOLOGY/SIGNIFICANT FINDINGS: 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.
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spelling pubmed-28932062010-07-01 Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices Xin, Yurong Chanrion, Benjamin Liu, Meng-Min Galfalvy, Hanga Costa, Ramiro Ilievski, Boro Rosoklija, Gorazd Arango, Victoria Dwork, Andrew J. Mann, J. John Tycko, Benjamin Haghighi, Fatemeh PLoS One Research Article 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. METHODOLOGY/SIGNIFICANT FINDINGS: 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. Public Library of Science 2010-06-28 /pmc/articles/PMC2893206/ /pubmed/20596539 http://dx.doi.org/10.1371/journal.pone.0011357 Text en Xin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xin, Yurong
Chanrion, Benjamin
Liu, Meng-Min
Galfalvy, Hanga
Costa, Ramiro
Ilievski, Boro
Rosoklija, Gorazd
Arango, Victoria
Dwork, Andrew J.
Mann, J. John
Tycko, Benjamin
Haghighi, Fatemeh
Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
title Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
title_full Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
title_fullStr Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
title_full_unstemmed Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
title_short Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices
title_sort genome-wide divergence of dna methylation marks in cerebral and cerebellar cortices
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893206/
https://www.ncbi.nlm.nih.gov/pubmed/20596539
http://dx.doi.org/10.1371/journal.pone.0011357
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