title: Monocyte enhancers are highly altered in systemic lupus erythematosus.
abstract: OBJECTIVE
  Histone modifications set transcriptional competency and can perpetuate pathologic expression patterns. We defined systemic lupus erythematosus (SLE)-specific changes in H3K4me3 and K3K27me3, histone marks of gene activation and repression, respectively.
  
  
  METHODS
  We used ChIP-seq to define histone modifications in monocytes from SLE patients and controls.
  
  
  RESULTS
  Both promoters and enhancers exhibited significant changes in histone methylation in SLE. Regions with differential H3K4me3 in SLE were significantly enriched in potential interferon-related transcription factor binding sites and pioneer transcription factor sites.
  
  
  CONCLUSIONS
  Enhancer activation defines the character of the cell and our data support extensive disease effects in monocytes, a particularly plastic lineage. Type I interferons not only drive altered gene expression but may also alter the character of the cell through chromatin modifications.
authors.affiliation: Division of Allergy & Immunology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Shi
authors.affiliation: The Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA 1910, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Allergy & Immunology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yiu Tak
authors.initials: YT
authors.lastname: Leung
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Petri
authors.affiliation: Division of Allergy & Immunology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D001665:Binding Sites; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D005260:Female; D005786:Gene Expression Regulation; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008745:Methylation; D009000:Monocytes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
chemical_list: D006657:Histones; D050856:Interferon Regulatory Factor-1; D014157:Transcription Factors; D007372:Interferons; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
keywords: IRF1; enhancer; epigenome; histone methylation; interferon; lupus