The DNA methylome and transcriptome of different brain regions in schizophrenia and bipolar disorder

Yun Xiao, Cynthia Camarillo, Yanyan Ping, Tania Bedard Arana, Hongying Zhao, Peter M. Thompson, Chaohan Xu, Bin Brenda Su, Huihui Fan, Javier Ordonez, Li Wang, Chunxiang Mao, Yunpeng Zhang, Dianne Cruz, Michael A. Escamilla, Xia Li, Chun Xu

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Extensive changes in DNA methylation have been observed in schizophrenia (SC) and bipolar disorder (BP), and may contribute to the pathogenesis of these disorders. Here, we performed genome-scale DNA methylation profiling using methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) on two brain regions (including frontal cortex and anterior cingulate) in 5 SC, 7 BP and 6 normal subjects. Comparing with normal controls, we identified substantial differentially methylated regions (DMRs) in these two brain regions of SC and BP. To our surprise, different brain regions show completely distinct distributions of DMRs across the genomes. In frontal cortex of both SC and BP subjects, we observed widespread hypomethylation as compared to normal controls, preferentially targeting the terminal ends of the chromosomes. In contrast, in anterior cingulate, both SC and BP subjects displayed extensive gain of methylation. Notably, in these two brain regions of SC and BP, only a few DMRs overlapped with promoters, whereas a greater proportion occurs in introns and intergenic regions. Functional enrichment analysis indicated that important psychiatric disorder-related biological processes such as neuron development, differentiation and projection may be altered by epigenetic changes located in the intronic regions. Transcriptome analysis revealed consistent dysfunctional processes with those determined by DMRs. Furthermore, DMRs in the same brain regions from SC and BP could successfully distinguish BP and/or SC from normal controls while differentially expressed genes could not. Overall, our results support a major role for brain-region-dependent aberrant DNA methylation in the pathogenesis of these two disorders.

Original languageEnglish (US)
Article numbere95875
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 28 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Xiao, Y., Camarillo, C., Ping, Y., Arana, T. B., Zhao, H., Thompson, P. M., Xu, C., Su, B. B., Fan, H., Ordonez, J., Wang, L., Mao, C., Zhang, Y., Cruz, D., Escamilla, M. A., Li, X., & Xu, C. (2014). The DNA methylome and transcriptome of different brain regions in schizophrenia and bipolar disorder. PloS one, 9(4), [e95875]. https://doi.org/10.1371/journal.pone.0095875