title: A subset of methylated CpG sites differentiate psoriatic from normal skin.
abstract: Psoriasis is a chronic inflammatory immune-mediated disorder affecting the skin and other organs including joints. Over 1,300 transcripts are altered in psoriatic involved skin compared with normal skin. However, to our knowledge, global epigenetic profiling of psoriatic skin is previously unreported. Here, we describe a genome-wide study of altered CpG methylation in psoriatic skin. We determined the methylation levels at 27,578 CpG sites in skin samples from individuals with psoriasis (12 involved, 8 uninvolved) and 10 unaffected individuals. CpG methylation of involved skin differed from normal skin at 1,108 sites. Twelve mapped to the epidermal differentiation complex, upstream or within genes that are highly upregulated in psoriasis. Hierarchical clustering of 50 of the top differentially methylated (DM) sites separated psoriatic from normal skin samples with uninvolved skin exhibiting intermediate methylation. CpG sites where methylation was correlated with gene expression are reported. Sites with inverse correlations between methylation and nearby gene expression include those of KYNU, OAS2, S100A12, and SERPINB3, whose strong transcriptional upregulation is an important discriminator of psoriasis. Pyrosequencing of bisulfite-treated DNA from skin biopsies at three DM loci confirmed earlier findings and revealed reversion of methylation levels toward the non-psoriatic state after 1 month of anti-TNF-α therapy.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Elisha D O
authors.initials: ED
authors.lastname: Roberson
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Caitriona
authors.initials: C
authors.lastname: Ryan
authors.forename: Cailin E
authors.initials: CE
authors.lastname: Joyce
authors.forename: Shenghui
authors.initials: S
authors.lastname: Duan
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Ann
authors.initials: A
authors.lastname: Martin
authors.forename: Wilson
authors.initials: W
authors.lastname: Liao
authors.forename: Alan
authors.initials: A
authors.lastname: Menter
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D001483:Base Sequence; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D009418:S100 Proteins / Q000096:biosynthesis; D000067616:S100A12 Protein; D017422:Sequence Analysis, DNA; D015843:Serpins / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D000068879:Adalimumab
references.citation: Reprod Biol Endocrinol. 2009 Jun 05;7:59
references.pmid: 19500360
references.citation: Mol Cell Biol. 2005 Dec;25(24):11184-90
references.pmid: 16314537
references.citation: Bioinformatics. 2005 Jun 1;21(11):2789-90
references.pmid: 15797915
references.citation: Cell. 1985 Jan;40(1):91-9
references.pmid: 2981636
references.citation: J Invest Dermatol. 2004 Mar;122(3):717-21
references.pmid: 15086558
references.citation: BMC Bioinformatics. 2010 Nov 30;11:587
references.pmid: 21118553
references.citation: PLoS One. 2010 Apr 20;5(4):e10247
references.pmid: 20422035
references.citation: Reproduction. 2004 Jun;127(6):643-51
references.pmid: 15175501
references.citation: Bioinformatics. 2008 Jul 1;24(13):1547-8
references.pmid: 18467348
references.citation: Nat Genet. 2006 Dec;38(12):1378-85
references.pmid: 17072317
references.citation: Br J Dermatol. 2005 Mar;152(3):489-504
references.pmid: 15787818
references.citation: Carcinogenesis. 2006 Dec;27(12):2409-23
references.pmid: 16952911
references.citation: Br J Dermatol. 2006 Jul;155(1):62-6
references.pmid: 16792753
references.citation: Autoimmunity. 2008 May;41(4):278-86
references.pmid: 18432408
references.citation: PLoS One. 2010 Nov 02;5(11):e13784
references.pmid: 21072176
references.citation: Am J Pathol. 2007 Jul;171(1):32-42
references.pmid: 17591951
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D876-82
references.pmid: 20959295
references.citation: Genomics. 1993 Oct;18(1):92-9
references.pmid: 8276421
references.citation: Endocrinology. 2011 May;152(5):2100-12
references.pmid: 21343250
references.citation: J Allergy Clin Immunol. 2003 Dec;112(6):1195-202
references.pmid: 14657882
references.citation: Nat Genet. 2005 Aug;37(8):899-905
references.pmid: 16007089
references.citation: Oncogene. 2010 Dec 2;29(48):6390-401
references.pmid: 20802525
references.citation: Nat Genet. 2005 Aug;37(8):853-62
references.pmid: 16007088
references.citation: Nat Genet. 2009 Feb;41(2):178-186
references.pmid: 19151715
references.citation: J Am Acad Dermatol. 2008 Jan;58(1):106-15
references.pmid: 17936411
references.citation: Nature. 2007 May 24;447(7143):425-32
references.pmid: 17522676
references.citation: Bioinformatics. 2002 Dec;18(12):1600-8
references.pmid: 12490444
references.citation: J Mol Med (Berl). 2006 Feb;84(2):175-82
references.pmid: 16389548
references.citation: EMBO J. 2006 Mar 8;25(5):1081-92
references.pmid: 16498406
references.citation: J Invest Dermatol. 2010 Jul;130(7):1829-40
references.pmid: 20220767
references.citation: Nat Rev Immunol. 2005 Sep;5(9):699-711
references.pmid: 16138103
references.citation: Br J Dermatol. 2005 May;152(5):1091-2
references.pmid: 15888191
references.citation: Ann Dermatol. 2009 Aug;21(3):237-42
references.pmid: 20523796
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7
references.pmid: 16432200
references.citation: Diabetologia. 2010 Jun;53(6):1164-73
references.pmid: 20238096
references.citation: Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R47-58
references.pmid: 15809273
references.citation: J Allergy Clin Immunol. 2009 Dec;124(6):1235-1244.e58
references.pmid: 20004782
references.citation: Nat Immunol. 2003 Mar;4(3):208-9
references.pmid: 12605226
references.citation: J Am Acad Dermatol. 2007 Jan;56(1):31.e1-15
references.pmid: 17097378
references.citation: Genome Biol. 2011;12(1):R10
references.pmid: 21251332
references.citation: J Invest Dermatol. 2009 Jan;129(1):79-88
references.pmid: 18633443
references.citation: Biotechniques. 2003 Jul;35(1):146-50
references.pmid: 12866414
references.citation: Hum Mol Genet. 2001 Aug 15;10(17):1793-805
references.pmid: 11532989
references.citation: Genome Biol. 2004;5(10):R80
references.pmid: 15461798
references.citation: Nat Rev Immunol. 2009 Feb;9(2):91-105
references.pmid: 19151746
references.citation: Genome Res. 2009 Aug;19(8):1462-70
references.pmid: 19491193
references.citation: Genome Res. 2006 Mar;16(3):383-93
references.pmid: 16449502
references.citation: Hum Genet. 2002 Oct;111(4-5):310-3
references.pmid: 12384771
references.citation: Curr Biol. 1993 Jun 1;3(6):384-6
references.pmid: 15335739
references.citation: Pharmacogenomics J. 2001;1(4):272-87
references.pmid: 11911124
references.citation: Neurosci Biobehav Rev. 2009 Apr;33(4):593-600
references.pmid: 18430469
references.citation: Nat Immunol. 2003 Mar;4(3):235-40
references.pmid: 12548284
references.citation: Trends Immunol. 2004 Jun;25(6):295-305
references.pmid: 15145319
references.citation: Semin Reprod Med. 2009 Sep;27(5):380-90
references.pmid: 19711248
references.citation: Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii18-23; discussion ii24-5
references.pmid: 15708928
references.citation: Genes Dev. 2002 Jan 1;16(1):6-21
references.pmid: 11782440
references.citation: Genome Res. 2010 Sep;20(9):1271-8
references.pmid: 20631049
references.citation: Physiol Genomics. 2003 Mar 18;13(1):69-78
references.pmid: 12644634
references.citation: J Histochem Cytochem. 2003 May;51(5):675-85
references.pmid: 12704215