title: Chromatin landscapes and genetic risk in systemic lupus.
abstract: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest.
  
  
  
  We used chromatin immunoprecipitation followed by sequencing to identify epigenetic marks associated with enhancer function in adult neutrophils to determine whether enhancer-associated histone marks were enriched within the linkage disequilibrium (LD) blocks encompassing the 46 SNPs of interest. We also interrogated available data in Roadmap Epigenomics for CD4+T cells and CD19+B cells to identify these same elements in lymphoid cells.
  
  
  
  All three cell types demonstrated enrichment of enhancer-associated histone marks compared with genomic background within LD blocks encoded by SLE-associated SNPs. In addition, within the promoter regions of these LD blocks, all three cell types demonstrated enrichment for transcription factor binding sites above genomic background. In CD19+B cells, all but one of the LD blocks of interest were also enriched for enhancer-associated histone marks.
  
  
  
  Much of the genetic risk for SLE lies within or near genomic regions of disease-relevant cells that are enriched for epigenetic marks associated with enhancer function. Elucidating the specific roles of these noncoding elements within these cell-type-specific genomes will be crucial to our understanding of SLE pathogenesis.
authors.affiliation: Division of Pediatric Rheumatology, Steven and Alexandra Cohen Children's Medical Center, 1991 Marcus Avenue, Suite M100, Lake Success, NY, 11042, USA. jhuiyuen@nshs.edu.|Department of Pediatrics, Hofstra-Northwell School of Medicine, Hempstead, NY, 11549, USA. jhuiyuen@nshs.edu.
authors.forename: Joyce S
authors.initials: JS
authors.lastname: Hui-Yuen
authors.affiliation: Department of Biochemistry, University at Buffalo, Buffalo, NY, 14203, USA.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, University at Buffalo, Buffalo, NY, 14203, USA.
authors.forename: Lai Ping
authors.initials: LP
authors.lastname: Wong
authors.affiliation: Department of Pediatrics, University at Buffalo, Buffalo, NY, 14203, USA.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, University at Buffalo, Buffalo, NY, 14203, USA.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, and Genetics, Genomics, and Bioinformatics Program, University at Buffalo, Buffalo, NY, 14203, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Genetics, Genomics, and Bioinformatics Program, University at Buffalo, Buffalo, NY, 14203, USA.
authors.forename: James N
authors.initials: JN
authors.lastname: Jarvis
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D002843:Chromatin
keywords: Enhancers; Genetics; Lymphocytes; Neutrophils; Systemic lupus erythematosus