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Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA.
Mowel, Walter K; McCright, Sam J; Kotzin, Jonathan J; Collet, Magalie A; Uyar, Asli; Chen, Xin; DeLaney, Alexandra; Spencer, Sean P; Virtue, Anthony T; Yang, EnJun; Villarino, Alejandro; Kurachi, Makoto; Dunagin, Margaret C; Pritchard, Gretchen Harms; Stein, Judith; Hughes, Cynthia; Fonseca-Pereira, Diogo; Veiga-Fernandes, Henrique; Raj, Arjun; Kambayashi, Taku; Brodsky, Igor E; O'Shea, John J; Wherry, E John; Goff, Loyal A; Rinn, John L; Williams, Adam; Flavell, Richard A; Henao-Mejia, Jorge.
Affiliation
  • Mowel WK; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • McCright SJ; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Kotzin JJ; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Collet MA; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Uyar A; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Chen X; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
  • DeLaney A; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Spencer SP; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Virtue AT; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Yang E; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Villarino A; Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
  • Kurachi M; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Dunagin MC; School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Pritchard GH; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Stein J; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06510, USA.
  • Hughes C; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06510, USA.
  • Fonseca-Pereira D; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisbon, Portugal.
  • Veiga-Fernandes H; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisbon, Portugal; Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal.
  • Raj A; School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Kambayashi T; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Brodsky IE; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • O'Shea JJ; Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
  • Wherry EJ; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Goff LA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Rinn JL; Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Williams A; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genomic Sciences, University of Connecticut Health Center, Farmington, CT 06032, USA. Electronic address: adam.williams@jax.org.
  • Flavell RA; School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: richard.flavell@yale.edu.
  • Henao-Mejia J; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Transplant Immunology, Department of Pathology and Laboratory Medicine
Immunity ; 47(3): 435-449.e8, 2017 09 19.
Article in En | MEDLINE | ID: mdl-28930659
ABSTRACT
Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs. Moreover, the Rroid locus, but not the lncRNA itself, controlled the identity and function of ILC1s by promoting chromatin accessibility and deposition of STAT5 at the promoter of Id2 in response to interleukin (IL)-15. Thus, non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphocytes / Regulatory Sequences, Nucleic Acid / Gene Expression Regulation / RNA, Long Noncoding / Immunity, Innate Type of study: Prognostic_studies Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2017 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphocytes / Regulatory Sequences, Nucleic Acid / Gene Expression Regulation / RNA, Long Noncoding / Immunity, Innate Type of study: Prognostic_studies Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2017 Document type: Article Affiliation country: