Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome

Wei Xie, Cathy L. Barr*, Audrey Kim, Feng Yue, Ah Young Lee, James Eubanks, Emma L. Dempster, Bing Ren

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

434 Scopus citations

Abstract

Differential methylation of the two parental genomes in placental mammals is essential for genomic imprinting and embryogenesis. To systematically study this epigenetic process, we have generated a base-resolution, allele-specific DNA methylation (ASM) map in the mouse genome. We find parent-of-origin dependent (imprinted) ASM at 1,952 CG dinucleotides. These imprinted CGs form 55 discrete clusters including virtually all known germline differentially methylated regions (DMRs) and 23 previously unknown DMRs, with some occurring at microRNA genes. We also identify sequence-dependent ASM at 131,765 CGs. Interestingly, methylation at these sites exhibits a strong dependence on the immediate adjacent bases, allowing us to define a conserved sequence preference for the mammalian DNA methylation machinery. Finally, we report a surprising presence of non-CG methylation in the adult mouse brain, with some showing evidence of imprinting. Our results provide a resource for understanding the mechanisms of imprinting and allele-specific gene expression in mammalian cells.

Original languageEnglish (US)
Pages (from-to)816-831
Number of pages16
JournalCell
Volume148
Issue number4
DOIs
StatePublished - Feb 17 2012

Funding

We thank Drs. Ryan Lister and Joseph Ecker for sharing the MethylC-Seq protocol and for valuable input on the experimental design. We are grateful to Dr. Paul Soloway for comments on the manuscript, Dr. Wei Wang for discussions, Ms. Lee Edsall and Samantha Kuan for technical support in deep sequencing, Richard Logan, Yu Feng, and Lissette Gomez for technical support in dissection of frontal cortex and extraction of DNA/RNA, Karen Wigg for initial RNA-Seq bioinformatics support, and members of the Ren laboratory for discussions. This study was funded in part by grants from the Krembil Seed Development Fund (C.L.B.), an Applied Biosystems (Life Technologies) 10K Genome Award (C.L.B.), and funding from the Ludwig Institute for Cancer Research (B.R.), the NIH Epigenomics Roadmap Project U01ES017166 (B.R.), and the National Human Genome Research Institute R01 HG003991 (B.R.).

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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