Proinflammatory Cytokine IL-12 Drives Dynamic STAT4-dependent Changes in RNA Polymerase II Landscape Within Natural Killer Cells — ASN Events
  1. Schedule
  2. Poster Session One
  3. Proinflammatory Cytokine IL-12 Drives Dynamic STAT4-dependent Changes in RNA Polymerase II Landscape Within Natural Killer Cells

Proinflammatory Cytokine IL-12 Drives Dynamic STAT4-dependent Changes in RNA Polymerase II Landscape Within Natural Killer Cells (#151)

Hyunu Kim 1 2 , Simon Grassmann 1 , Wilfred Wong 3 4 , Nicholas Adams 5 , Christina Leslie 3 , Inez Rogatsky 6 , Joseph Sun 1 7
  1. Immunology , Memorial Sloan Kettering Cancer Center, New York, USA
  2. Gerstner Sloan Kettering Graduate School, NEW YORK, United States
  3. Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, NEW YORK, New York, USA
  4. Computational Biology and Medicine, Tri-Institutional Training Program, NEW YORK, New York, USA
  5. Department of Pathology, New York University Grossman School of Medicine, NEW YORK, New York, USA
  6. Hospital for Special Surgery Research Institute, David Z. Rosensweig Genomics Center, NEW YORK, New York, USA
  7. Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, NEW YORK, New York, USA

Natural killer (NK) cells respond to inflammatory cytokines produced during infection by mounting a rapid innate immune response. However, the mechanism by which immediate effector genes, such as interferon gamma (Ifng), are regulated through RNA Polymerase II (Pol II) remain incompletely understood. In this study, we utilize Pol II cleavage under targets and release using nuclease sequencing (CUT&RUN) to analyze primary NK cells stimulated with proinflammatory cytokines at various timepoints. Cytokine treatment reveals a highly dynamic Pol II landscape, with interleukin-12 (IL-12) inducing substantial changes in Pol II localization mediated by the transcription factor STAT4, and one of the strongest IL-12 induced increase in Pol II binding is at Ifng. Mass spectrometry for STAT4 interacting proteins revealed the RNA helicase DDX5, which is required for optimal IFN-γ production following cytokine stimulation and modulates Pol II occupancy. Thus, our findings highlight STAT4-mediated regulation of Pol II as a critical mechanism driving the cytokine-induced response in NK cells.