title: Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences.
abstract: DNA methylation is a vital epigenetic mark that participates in establishing and maintaining chromatin structures and regulates gene transcription during mammalian development and cellular differentiation. Differences in epigenetic patterns between individuals may contribute to phenotypic variation and disease susceptibility; however, little is known about the extent of such variation or how different epigenetic patterns are established. Here we have compared DNA methylation profiles of macrophages from two inbred mouse strains (C57BL/6 and BALB/c) at 181 large genomic intervals that were selected based on differential gene expression patterns. Using a DNA methylation-dependent fractionation approach based on a combination of methyl-CpG immunoprecipitation and locus-wide tiling arrays, we identified several hundred differentially methylated regions, and simultaneously uncovered previously unrecognized genetic variability between both mouse strains at the studied loci. DNA sequence and methylation differences were validated by DNA sequencing and mass spectrometry analysis of bisulfite-treated DNA for a subset of regions. Importantly, we show that in F1 hybrids, the majority of strain-specific methylation patterns in somatic cells were maintained on the parental allele, regardless of their status in the male germ line. The common association of differentially methylated regions with sequence polymorphisms suggests that the genomic context determines the developmentally regulated epigenetic status at most nonimprinted regions of mammalian genomes.
authors.affiliation: Department of Hematology, University Hospital Regensburg, 93042 Regensburg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Schilling
authors.forename: Carol
authors.initials: C
authors.lastname: El Chartouni
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011110:Polymorphism, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
references.citation: Ann Inst Pasteur Immunol. 1987 Sep-Oct;138(5):744-9
references.pmid: 2964247
references.citation: Science. 2008 Oct 17;322(5900):434-8
references.pmid: 18787134
references.citation: Nat Genet. 2008 Jul;40(7):904-8
references.pmid: 18568024
references.citation: Nat Genet. 2008 Jul;40(7):909-14
references.pmid: 18500340
references.citation: Genome Res. 2009 Jul;19(7):1165-74
references.pmid: 19494038
references.citation: Cancer Res. 2006 Jun 15;66(12):6118-28
references.pmid: 16778185
references.citation: PLoS Genet. 2006 Apr;2(4):e49
references.pmid: 16604157
references.citation: Genes Dev. 2002 Jan 1;16(1):6-21
references.pmid: 11782440
references.citation: Hum Mol Genet. 2004 Jan 15;13(2):247-55
references.pmid: 14645199
references.citation: Hum Mol Genet. 2007 Mar 1;16(5):547-54
references.pmid: 17339271
references.citation: Am J Hum Genet. 2006 Jul;79(1):67-84
references.pmid: 16773567
references.citation: Nat Genet. 2008 May;40(5):663-9
references.pmid: 18425126
references.citation: Genomics. 2007 Sep;90(3):314-23
references.pmid: 17582736
references.citation: Nature. 2007 Aug 30;448(7157):1050-3
references.pmid: 17660834
references.citation: Nat Genet. 2007 Sep;39(9):1100-7
references.pmid: 17660819
references.citation: Immunobiology. 1993 Dec;189(5):419-35
references.pmid: 8125519
references.citation: Genome Biol. 2008;9(12):R182
references.pmid: 19099580
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references.pmid: 16009939
references.citation: Nat Genet. 2009 Feb;41(2):240-5
references.pmid: 19151718
references.citation: Trends Genet. 2002 Jul;18(7):348-51
references.pmid: 12127774
references.citation: Biochem Biophys Res Commun. 2002 Feb 8;290(5):1499-505
references.pmid: 11820791
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15785-90
references.pmid: 16243968
references.citation: Nat Genet. 2007 May;39(5):614-22
references.pmid: 17450140
references.citation: Nat Genet. 1999 Nov;23(3):314-8
references.pmid: 10545949