title: RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer.
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.
authors: Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 7610001, Israel.
authors: Ohad
authors: O
authors: Tarcic
authors: Molecular Carcinogenesis Group, Department of Histology-Embryology, School of Medicine, University of Athens, 11527 Athens, Greece.
authors: Ioannis S
authors: IS
authors: Pateras
authors: Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 7610001, Israel.
authors: Tomer
authors: T
authors: Cooks
authors: Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 7610001, Israel.
authors: Efrat
authors: E
authors: Shema
authors: The Lautenberg Center for General and Tumor Immunology, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors: Julia
authors: J
authors: Kanterman
authors: The Lautenberg Center for General and Tumor Immunology, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors: Hadas
authors: H
authors: Ashkenazi
authors: The Lautenberg Center for General and Tumor Immunology, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors: Hana
authors: H
authors: Boocholez
authors: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem 91120, Israel.
authors: Ayala
authors: A
authors: Hubert
authors: Department of Biological Services, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors: Ron
authors: R
authors: Rotkopf
authors: The Lautenberg Center for General and Tumor Immunology, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors: Michal
authors: M
authors: Baniyash
authors: Department of Immunology and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel; Department of Pathology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors: Eli
authors: E
authors: Pikarsky
authors: Molecular Carcinogenesis Group, Department of Histology-Embryology, School of Medicine, University of Athens, 11527 Athens, Greece; Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece; Faculty Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors: Vassilis G
authors: VG
authors: Gorgoulis
authors: Department of Molecular Cell Biology, The Weizmann Institute, Rehovot 7610001, Israel. Electronic address: moshe.oren@weizmann.ac.il.
authors: Moshe
authors: M
authors: Oren
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000276:immunology; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007249:Inflammation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000276:immunology; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D006657:Histones; D016328:NF-kappa B; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases