title: Role of CpG context and content in evolutionary signatures of brain DNA methylation.
abstract: DNA methylation is essential in brain function and behavior; therefore, understanding the role of DNA methylation in brain-based disorders begins with the study of DNA methylation profiles in normal brain. Determining the patterns and scale of methylation conservation and alteration in an evolutionary context enables the design of focused but effective methylation studies of disease states. We applied an enzymatic-based approach, Methylation Mapping Analysis by Paired-end Sequencing (Methyl-MAPS), which utilizes second-generation sequencing technology to provide an unbiased representation of genome-wide DNA methylation profiles of human and mouse brains. In this large-scale study, we assayed CpG methylation in cerebral cortex of neurologically and psychiatrically normal human postmortem specimens, as well as mouse forebrain specimens. Cross-species human-mouse DNA methylation conservation analysis shows that DNA methylation is not correlated with sequence conservation. Instead, greater DNA methylation conservation is correlated with increasing CpG density. In addition to CpG density, these data show that genomic context is a critical factor in DNA methylation conservation and alteration signatures throughout mammalian brain evolution. We identify key genomic features that can be targeted for identification of epigenetic loci that may be developmentally and evolutionarily conserved and wherein aberrations in DNA methylation patterns can confer risk for disease.
authors: Department of Psychiatry, Columbia University and The New York State Psychiatric Institute, New York, NY, USA.
authors: Yurong
authors: Y
authors: Xin
authors: Anne H
authors: AH
authors: O'Donnell
authors: Yongchao
authors: Y
authors: Ge
authors: Benjamin
authors: B
authors: Chanrion
authors: Maria
authors: M
authors: Milekic
authors: Gorazd
authors: G
authors: Rosoklija
authors: Aleksandar
authors: A
authors: Stankov
authors: Victoria
authors: V
authors: Arango
authors: Andrew J
authors: AJ
authors: Dwork
authors: Jay A
authors: JA
authors: Gingrich
authors: Fatemeh G
authors: FG
authors: Haghighi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D019143:Evolution, Molecular; D005260:Female; D020869:Gene Expression Profiling; D016678:Genome; D023281:Genomics; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged