TY - JOUR
T1 - Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome
AU - Xie, Wei
AU - Barr, Cathy L.
AU - Kim, Audrey
AU - Yue, Feng
AU - Lee, Ah Young
AU - Eubanks, James
AU - Dempster, Emma L.
AU - Ren, Bing
N1 - Funding Information:
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.).
PY - 2012/2/17
Y1 - 2012/2/17
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2011.12.035
DO - 10.1016/j.cell.2011.12.035
M3 - Article
C2 - 22341451
AN - SCOPUS:84857331867
SN - 0092-8674
VL - 148
SP - 816
EP - 831
JO - Cell
JF - Cell
IS - 4
ER -