Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation

Li, X., Baker-Andresen, D., Zhao, Q., Marshall, V. and Bredy, T. W. (2014) Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation. Genes, Brain and Behavior, 13 7: 721-731. doi:10.1111/gbb.12150

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Author Li, X.
Baker-Andresen, D.
Zhao, Q.
Marshall, V.
Bredy, T. W.
Title Methyl CpG Binding Domain Ultra-Sequencing: a novel method for identifying inter-individual and cell-type-specific variation in DNA methylation
Journal name Genes, Brain and Behavior   Check publisher's open access policy
ISSN 1601-1848
1601-183X
Publication date 2014-09-01
Year available 2014
Sub-type Article (original research)
DOI 10.1111/gbb.12150
Volume 13
Issue 7
Start page 721
End page 731
Total pages 11
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Experience-dependent changes in DNA methylation can exert profound effects on neuronal function and behaviour. A single learning event can induce a variety of DNA modifications within the neuronal genome, some of which may be common to all individuals experiencing the event, whereas others may occur in a subset of individuals. Variations in experience-induced DNA methylation may subsequently confer increased vulnerability or resilience to the development of neuropsychiatric disorders. However, the detection of experience-dependent changes in DNA methylation in the brain has been hindered by the interrogation of heterogeneous cell populations, regional differences in epigenetic states and the use of pooled tissue obtained from multiple individuals. Methyl CpG Binding Domain Ultra-Sequencing (MBD Ultra-Seq) overcomes current limitations on genome-wide epigenetic profiling by incorporating fluorescence-activated cell sorting and sample-specific barcoding to examine cell-type-specific CpG methylation in discrete brain regions of individuals. We demonstrate the value of this method by characterizing differences in 5-methylcytosine (5mC) in neurons and non-neurons of the ventromedial prefrontal cortex of individual adult C57BL/6 mice, using as little as 50 ng of genomic DNA per sample. We find that the neuronal methylome is characterized by greater CpG methylation as well as the enrichment of 5mC within intergenic loci. In conclusion, MBD Ultra-Seq is a robust method for detecting DNA methylation in neurons derived from discrete brain regions of individual animals. This protocol will facilitate the detection of experience-dependent changes in DNA methylation in a variety of behavioural paradigms and help identify aberrant experience-induced DNA methylation that may underlie risk and resiliency to neuropsychiatric disease.
Keyword DNA methylation
Genome-wide
MBD
NeuN
Neuron
Next-generation sequencing
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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