DNA methylation profile dynamics of tissue-dependent and differentially methylated regions during mouse brain development

Keiji Hirabayashi, Kunio Shiota, Shintaro Yagi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Tissues and their component cells have unique DNA methylation profiles comprising DNA methylation patterns of tissue-dependent and differentially methylated regions (T-DMRs). Previous studies reported that DNA methylation plays crucial roles in cell differentiation and development. Here, we investigated the genome-wide DNA methylation profiles of mouse neural progenitors derived from different developmental stages using HpyCH4IV, a methylation-sensitive restriction enzyme that recognizes ACGT residues, which are uniformly distributed across the genome.Results: Using a microarray-based genome-wide DNA methylation analysis system focusing on 8.5-kb regions around transcription start sites (TSSs), we analyzed the DNA methylation profiles of mouse neurospheres derived from telencephalons at embryonic days 11.5 (E11.5NSph) and 14.5 (E14.5NSph) and the adult brain (AdBr). We identified T-DMRs with different DNA methylation statuses between E11.5NSph and E14.5NSph at genes involved in neural development and/or associated with neurological disorders in humans, such as Dclk1, Nrcam, Nfia, and Ntng1. These T-DMRs were located not only within 2 kb but also distal (several kbs) from the TSSs, and those hypomethylated in E11.5NSph tended to be in CpG island (CGI-) associated genes. Most T-DMRs that were hypomethylated in neurospheres were also hypomethylated in the AdBr. Interestingly, among the T-DMRs hypomethylated in the progenitors, there were T-DMRs that were hypermethylated in the AdBr. Although certain genes, including Ntng1, had hypermethylated T-DMRs 5' upstream, we identified hypomethylated T-DMRs in the AdBr, 3' downstream from their TSSs. This observation could explain why Ntng1 was highly expressed in the AdBr despite upstream hypermethylation.Conclusion: Mouse adult brain DNA methylation and gene expression profiles could be attributed to developmental dynamics of T-DMRs in neural-related genes.

Original languageEnglish
Article number82
JournalBMC Genomics
Volume14
Issue number1
DOIs
Publication statusPublished - 2013 Feb 6
Externally publishedYes

Fingerprint

DNA Methylation
Brain
Transcription Initiation Site
Genome
Genes
Telencephalon
CpG Islands
Cellular Structures
Nervous System Diseases
Transcriptome
Methylation
Cell Differentiation

Keywords

  • DNA methylation
  • Neural progenitor cells
  • Tissue-dependent and differentially methylated region

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

DNA methylation profile dynamics of tissue-dependent and differentially methylated regions during mouse brain development. / Hirabayashi, Keiji; Shiota, Kunio; Yagi, Shintaro.

In: BMC Genomics, Vol. 14, No. 1, 82, 06.02.2013.

Research output: Contribution to journalArticle

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