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DNA methylation as a transcriptional regulator of the immune system

  • Author Footnotes
    1 1These authors contributed equally.
    Luisa Morales-Nebreda
    Footnotes
    1 1These authors contributed equally.
    Affiliations
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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  • Author Footnotes
    1 1These authors contributed equally.
    Fred S. McLafferty
    Footnotes
    1 1These authors contributed equally.
    Affiliations
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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  • Author Footnotes
    2 2Benjamin D. Singer, MD, is an Assistant Professor in the Division of Pulmonary and Critical Care Medicine at Northwestern University Feinberg School of Medicine. Dr. Singer is a physician-scientist working to understand how DNA methylation controls the immune system, particularly T cells, in the setting of lung disease and aging.
    Benjamin D. Singer
    Correspondence
    Reprint requests: Benjamin D. Singer, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Biochemistry and Molecular Genetics, Simpson Querrey Center for Epigenetics, Northwestern University, Feinberg School of Medicine, 240 East Huron Street, Suite M-300, Chicago, IL 60611;
    Footnotes
    2 2Benjamin D. Singer, MD, is an Assistant Professor in the Division of Pulmonary and Critical Care Medicine at Northwestern University Feinberg School of Medicine. Dr. Singer is a physician-scientist working to understand how DNA methylation controls the immune system, particularly T cells, in the setting of lung disease and aging.
    Affiliations
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois

    Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, Illinois

    Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
    Search for articles by this author
  • Author Footnotes
    1 1These authors contributed equally.
    2 2Benjamin D. Singer, MD, is an Assistant Professor in the Division of Pulmonary and Critical Care Medicine at Northwestern University Feinberg School of Medicine. Dr. Singer is a physician-scientist working to understand how DNA methylation controls the immune system, particularly T cells, in the setting of lung disease and aging.
Published:August 09, 2018DOI:https://doi.org/10.1016/j.trsl.2018.08.001
      DNA methylation is a dynamic epigenetic modification with a prominent role in determining mammalian cell development, lineage identity, and transcriptional regulation. Primarily linked to gene silencing, novel technologies have expanded the ability to measure DNA methylation on a genome-wide scale and uncover context-dependent regulatory roles. The immune system is a prototypic model for studying how DNA methylation patterning modulates cell type- and stimulus-specific transcriptional programs. Preservation of host defense and organ homeostasis depends on fine-tuned epigenetic mechanisms controlling myeloid and lymphoid cell differentiation and function, which shape innate and adaptive immune responses. Dysregulation of these processes can lead to human immune system pathology as seen in blood malignancies, infections, and autoimmune diseases. Identification of distinct epigenotypes linked to pathogenesis carries the potential to validate therapeutic targets in disease prevention and management.

      Abbreviations:

      AID/APOBEC (activation-induced deaminase/apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like), AML (acute myeloid leukemia), AP (apyrimidinic), BER (base excision repair), CD4−CD8− (DN, double-negative cells), CD4+CD8+ (DP, double-positive cells), ChIP (chromatin immunoprecipitation), CHIP (clonal hematopoiesis of indeterminate potential), CLP (common lymphoid progenitors), CNS (conserved noncoding DNA sequences), CMP (common myeloid progenitors), CpG dinucleotides (5′-cytosine-phosphate-guanine-3′), CTCF (CCCTC-binding factor), CTLA-4 (cytotoxic T lymphocyte antigen 4), Dam (DNA adenine methyltransferases), DNMT (DNA methyltransferase), DNMTI (DNA methyltransferase inhibitor), EWAS (epigenome-wide association studies), FOXP3 (Forkhead box P3), GWAS (genome-wide association studies), HDAC (histone deacetylase), IDH 1 and IDH 2 (isocitrate dehydrogenase 1 and 2), IPEX (immune dysregulation, polyendocrinopathy, enteropathy X-linked), LPS (lipopolysaccharide), MBD (methyl-CpG binding domain), mCH (non-CG methylation), MDS (myelodysplastic syndrome), MeDIP (methyl-DNA immunoprecipitation), meQTLs (methylation quantitative trait loci), MLL (mixed lineage leukemia), MPP (multipotent progenitors), NMP1 (nucleophosmin 1), NSCLC (non–small cell lung cancer), PD-1 (programmed death-1), RA (rheumatoid arthritis), RRBS (reduced representation bisulfite sequencing), SLE (systemic lupus erythematosus), SNPs (single-nucleotide polymorphisms), TDG (thymine DNA glycosylase), TET (ten-eleven translocation), TGF-β (transforming growth factor-β), Th (helper T), Treg cells (regulatory T cells), UHRF (proteins, ubiquitin-like, containing PHD and RING finger domains), WGBS (whole-genome bisulfite sequencing), 5caC (5-carboxylcytosine), 5fC (5-formylcytosine), 2-HG (2-hydroxyglutarate), 5hmC (5-hydroxymethylcytosine), 5hmU (5-hydroxymethyluracil), 5mC (5-methylcytosine), 5mU (5-methyluracil), α-KG (α-ketoglutarate.)
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