title: Distribution of a marker of germline methylation differs between major families of transposon-derived repeats in the human genome.
abstract: A potential relationship between transposon-derived repeats (TDR) and human germline methylation is of biological importance since many genes are flanked by TDR and methylation could affect the expression of nearby genes. Furthermore, DNA methylation has been suggested as a global defense mechanism against genome instability threatened by TDR. We studied the correlation between the density of HapMap methyl-associated SNPs (mSNPs), a marker of germline methylation, and proportion of TDR. After correcting for confounding variables, we found a negative correlation between proportion of Alu repeats and mSNP density for 125-1000 kb windows. Similar results were found for the most active subgroup of repeats. In contrast, a negative correlation between proportion of L1 repeats and mSNP density was found only in the larger 1000 kb windows. Using methylation data on germ cells (sperm) from the Human Epigenome Project, we found a lower proportion of Alu repeats adjacent (3-15 kb) to hypermethylated amplicons. On the contrary, there was a higher proportion of L1 repeats in the 3-5 kb of sequence flanking hypermethylated amplicons but not in the 10-15 kb flanks. Our data indicate a differential response to the major repeat families and that DNA methylation is unlikely to be a uniform global defense system against all TDR. It appears to play a role for the L1 subgroup, with sequences adjacent to L1 repeats methylated in response to their proximity. In contrast, sequences adjacent to Alu repeats appear to be hypomethylated, arguing against a role of methylation in germline defense against those elements.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, IS-101, and Department of Genetics and Molecular Medicine, Landspitali-University Hospital, Reykjavik, IS-101, Iceland.
authors.forename: Martin I
authors.initials: MI
authors.lastname: Sigurdsson
authors.forename: Albert V
authors.initials: AV
authors.lastname: Smith
authors.forename: Hans T
authors.initials: HT
authors.lastname: Bjornsson
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Jonsson
mesh_terms: D020087:Alu Elements; D019175:DNA Methylation; D004251:DNA Transposable Elements; D015894:Genome, Human; D060148:HapMap Project; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012091:Repetitive Sequences, Nucleic Acid; D013094:Spermatozoa
chemical_list: D004251:DNA Transposable Elements
references.citation: J Hum Genet. 1998;43(2):77-84
references.pmid: 9621510
references.citation: Genome Res. 2002 Aug;12(8):1246-56
references.pmid: 12176932
references.citation: Genes Dev. 1987 Dec;1(10):1039-46
references.pmid: 3428592
references.citation: Mutat Res. 2007 Mar 1;616(1-2):46-59
references.pmid: 17157332
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
references.pmid: 14681465
references.citation: Trends Genet. 1997 Dec;13(12):469-72
references.pmid: 9433135
references.citation: Nature. 2006 Jul 13;442(7099):199-202
references.pmid: 16751776
references.citation: Genetics. 1991 Jun;128(2):471-86
references.pmid: 1649073
references.citation: Trends Genet. 1997 Aug;13(8):335-40
references.pmid: 9260521
references.citation: Gene. 2007 Apr 1;390(1-2):199-205
references.pmid: 17079095
references.citation: Genome Res. 2009 Apr;19(4):581-9
references.pmid: 19158364
references.citation: Gene. 2007 Apr 1;390(1-2):153-65
references.pmid: 17141428
references.citation: Gene. 2006 Mar 29;370:43-50
references.pmid: 16446059
references.citation: Heredity (Edinb). 2010 Jul;105(1):92-104
references.pmid: 20442734
references.citation: Science. 2005 Oct 14;310(5746):321-4
references.pmid: 16224025
references.citation: J Biol Chem. 1997 Aug 29;272(35):22322-9
references.pmid: 9268383
references.citation: Nucleic Acids Res. 1994 Nov 25;22(23):5121-7
references.pmid: 7800508
references.citation: Genome Res. 2004 Jul;14(7):1221-31
references.pmid: 15197167
references.citation: Gene. 2007 Apr 1;390(1-2):190-8
references.pmid: 17067767
references.citation: Cytogenet Genome Res. 2005;110(1-4):462-7
references.pmid: 16093699
references.citation: Mol Cell Biol. 1993 Aug;13(8):4523-30
references.pmid: 8336699
references.citation: Am J Hum Genet. 2006 Apr;78(4):671-9
references.pmid: 16532396
references.citation: Nature. 1985 Jun 13-19;315(6020):594-7
references.pmid: 2989695
references.citation: Nature. 2010 Apr 8;464(7290):927-31
references.pmid: 20164836
references.citation: Nature. 1983 Jan 6;301(5895):89-92
references.pmid: 6185846
references.citation: Curr Opin Genet Dev. 1998 Jun;8(3):343-50
references.pmid: 9690999
references.citation: Science. 1991 Dec 20;254(5039):1805-8
references.pmid: 1662412
references.citation: Nature. 2009 Nov 19;462(7271):315-22
references.pmid: 19829295
references.citation: Nat Genet. 2003 Sep;35(1):41-8
references.pmid: 12897783
references.citation: Genome Res. 2008 Mar;18(3):343-58
references.pmid: 18256243
references.citation: Environ Mol Mutagen. 1993;21(3):212-8
references.pmid: 8385004
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: J Mol Biol. 2004 Nov 26;344(3):675-82
references.pmid: 15533437
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: Genomics. 2009 May;93(5):434-40
references.pmid: 19442638
references.citation: JAMA. 2008 Jun 25;299(24):2877-83
references.pmid: 18577732
references.citation: Genome Dyn. 2006;1:104-115
references.pmid: 18724056
references.citation: PLoS Genet. 2008 Sep 26;4(9):e1000204
references.pmid: 18818740
references.citation: Mamm Genome. 2007 Apr;18(4):277-85
references.pmid: 17514347
references.citation: Oncogene. 2002 Aug 12;21(35):5388-93
references.pmid: 12154401
references.citation: Gene. 1997 Apr 21;189(2):227-34
references.pmid: 9168132
references.citation: Nucleic Acids Res. 2006 Jan 10;34(1):89-95
references.pmid: 16407327
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: Nat Genet. 2002 Dec;32(4):655-60
references.pmid: 12415270
references.citation: Nat Genet. 2006 Dec;38(12):1378-85
references.pmid: 17072317
references.citation: Mol Cell Biol. 2002 Jan;22(2):480-91
references.pmid: 11756544