@article{3085610,
    title = "RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer",
    author = "Tarcic, O. and Pateras, I.S. and Cooks, T. and Shema, E. and Kanterman, J. and Ashkenazi, H. and Boocholez, H. and Hubert, A. and Rotkopf, R. and Baniyash, M. and Pikarsky, E. and Gorgoulis, V.G. and Oren, M.",
    journal = "Cell Reports Medicine",
    year = "2016",
    volume = "14",
    number = "6",
    pages = "1462-1476",
    publisher = "Elsevier B.V.",
    doi = "10.1016/j.celrep.2016.01.020",
    keywords = "histone H2B;  protein RNF20;  transcription factor RelA;  tumor necrosis factor alpha;  ubiquitin protein ligase E3;  unclassified drug;  chromatin;  histone;  immunoglobulin enhancer binding protein;  RNF20 protein, human;  ubiquitin protein ligase, animal cell;  animal experiment;  animal tissue;  Article;  binding affinity;  cell activity;  colorectal cancer;  controlled study;  cytokine response;  disease association;  disease predisposition;  disease severity;  DNA damage;  down regulation;  exon;  gene;  gene targeting;  heterozygosity;  human;  human cell;  IL6 gene;  IL8 gene;  immunocompetent cell;  innate immunity;  mouse;  nonhuman;  priority journal;  protein binding;  protein function;  RNF20 gene;  T lymphocyte;  ubiquitination;  ulcerative colitis;  animal;  bone marrow cell;  chemistry;  chromatin;  colon;  Colorectal Neoplasms;  complication;  gene expression regulation;  genetic transcription;  genetics;  immunology;  inflammation;  male;  pathology;  signal transduction;  transgenic mouse;  ubiquitination;  ulcerative colitis, Animals;  Chromatin;  Colitis, Ulcerative;  Colon;  Colorectal Neoplasms;  Gene Expression Regulation, Neoplastic;  Histones;  Humans;  Inflammation;  Male;  Mice;  Mice, Transgenic;  Myeloid Cells;  NF-kappa B;  Signal Transduction;  T-Lymphocytes;  Transcription, Genetic;  Ubiquitin-Protein Ligases;  Ubiquitination",
    abstract = "Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20+/- mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings. © 2016 The Authors."
}