Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses Journal Article

Authors: Rapp, M.; Lau, C. M.; Adams, N. M.; Weizman, O. E.; O'Sullivan, T. E.; Geary, C. D.; Sun, J. C.
Article Title: Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses
Abstract: Natural killer (NK) cells are innate lymphocytes that have features of adaptive immunity such as clonal expansion and generation of long-lived memory. Interleukin-12 (IL-12) signaling through its downstream transcription factor signal transducer and activator of transcription 4 (STAT4) is required for the generation of memory NK cells after expansion. We identify gene loci that are highly enriched for STAT4 binding using chromatin immunoprecipitation sequencing for STAT4 and the permissive histone mark H3K4me3 in activated NK cells. We found that promoter regions of Runx1 and Runx3 are targets of STAT4 and that STAT4 binding during NK cell activation induces epigenetic modifications of Runx gene loci resulting in increased expression. Furthermore, specific ablation of Runx1, Runx3, or their binding partner Cbfb in NK cells resulted in defective clonal expansion and memory formation during viral infection, with evidence for Runx1-mediated control of a cell cycle program. Thus, our study reveals a mechanism whereby STAT4-mediated epigenetic control of individual Runx transcription factors promotes the adaptive behavior of antiviral NK cells.
Keywords: proteins; memory; differentiation; expression; regulatory t-cells; viral-infection; lineage; nk cells; stat4 activation; innate lymphoid-cells
Journal Title: Science Immunology
Volume: 2
Issue: 18
ISSN: 2470-9468
Publisher: Amer Assoc Advancement Science  
Date Published: 2017-12-08
Start Page: eaan3796
Language: English
ACCESSION: WOS:000434329200003
DOI: 10.1126/sciimmunol.aan3796
PUBMED: 29222089
PMCID: PMC6265048
Notes: Article -- UNSP eaan3796 -- Source: Wos
Citation Impact
MSK Authors
  1. Joseph C Sun
    94 Sun
  2. Moritz Enzo Rapp
    11 Rapp
  3. Clair   Geary
    13 Geary
  4. Nicholas M Adams
    17 Adams
  5. Colleen M Lau
    16 Lau