title: DNA methylome in human CD4+ T cells identifies transcriptionally repressive and non-repressive methylation peaks.
abstract: DNA methylation is an epigenetic mark that is critical in determining chromatin accessibility and regulating gene expression. This epigenetic mechanism has an important role in T-cell function. We used genome-wide methylation profiling to characterize the DNA methylome in primary human CD4+ T cells. We found that only 5% of CpG islands are methylated in CD4+ T cells, and that DNA methylation peak density is increased in subtelomeric chromosomal regions. We also found an inverse relationship between methylation peak density and chromosomal length. Our data indicate that DNA methylation in gene promoter regions is not always a repressive epigenetic mark. Indeed, about 27% of methylated genes are actively expressed in CD4+ T cells. We demonstrate that repressive methylation peaks are located closer to the transcription start site (TSS) compared with functionally non-repressive peaks (-893±110 bp versus -1342±218 bp (mean±s.e.m.), P-value <0.05). We also show that both a larger number and an increased CpG island density in promoter sequences predict transcriptional permissiveness of DNA methylation. TSS in the majority of genes with permissive DNA methylation peaks is in DNase I hypersensitive sites, indicating a failure of DNA methylation to induce chromatin inaccessibility in these loci.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, 73104, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hughes
authors.forename: R
authors.initials: R
authors.lastname: Webb
authors.forename: Y
authors.initials: Y
authors.lastname: Fei
authors.forename: J D
authors.initials: JD
authors.lastname: Wren
authors.forename: A H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016678:Genome; D006801:Humans; D024363:Transcription Initiation Site
chemical_list: D002843:Chromatin
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14412-7
references.pmid: 10588719
references.citation: Nature. 1993 Nov 25;366(6453):362-5
references.pmid: 8247133
references.citation: Nature. 1998 May 28;393(6683):386-9
references.pmid: 9620804
references.citation: Nat Genet. 1998 Jun;19(2):187-91
references.pmid: 9620779
references.citation: Nat Genet. 2009 Feb;41(2):178-186
references.pmid: 19151715
references.citation: Genes Immun. 2008 Jun;9(4):368-78
references.pmid: 18523434
references.citation: PLoS One. 2008 Feb 20;3(2):e1612
references.pmid: 18286169
references.citation: PLoS Biol. 2007 Feb;5(2):e38
references.pmid: 17298177
references.citation: Nature. 2009 Nov 19;462(7271):315-22
references.pmid: 19829295
references.citation: Science. 2001 Aug 10;293(5532):1089-93
references.pmid: 11498579
references.citation: Cell. 1999 Nov 24;99(5):451-4
references.pmid: 10589672
references.citation: Transl Res. 2009 Jan;153(1):4-10
references.pmid: 19100952
references.citation: PLoS Genet. 2007 Oct;3(10):2023-36
references.pmid: 17967063
references.citation: Cell. 2008 Jan 25;132(2):311-22
references.pmid: 18243105
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):671-8
references.pmid: 19139413
references.citation: Bioinformatics. 2004 Nov 22;20(17):3005-12
references.pmid: 15247106
references.citation: Science. 1981 Jan 23;211(4480):393-6
references.pmid: 6164095
references.citation: Eur J Immunol. 2007 May;37(5):1407-13
references.pmid: 17429846
references.citation: Nat Genet. 2007 Apr;39(4):457-66
references.pmid: 17334365
references.citation: Autoimmunity. 2008 May;41(4):245-52
references.pmid: 18432405
references.citation: Cold Spring Harb Symp Quant Biol. 1993;58:281-5
references.pmid: 7956040
references.citation: Cell. 2008 Dec 12;135(6):1144-1144.e1
references.pmid: 19070582
references.citation: Nat Genet. 2006 Dec;38(12):1378-85
references.pmid: 17072317