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Epigenetic activation during T helper 17 cell differentiation is mediated by Tripartite motif containing 28

Author

Listed:
  • Yu Jiang

    (Tsinghua University)

  • Ying Liu

    (Weill Cornell Medical College)

  • Huiping Lu

    (Tsinghua University)

  • Shao-Cong Sun

    (MD Anderson Cancer Center)

  • Wei Jin

    (Tsinghua University)

  • Xiaohu Wang

    (Tsinghua University)

  • Chen Dong

    (Tsinghua University
    Beijing Key Lab for Immunological Research on Chronic Diseases)

Abstract

Epigenetic regulation is important for T-cell fate decision. Although STAT3 is known to initiate Th17 differentiation program, the downstream mechanism is unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in Th17 cells is required for Th17-mediated cytokine production and experimental autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound regions overlap with almost all Th17-specific super-enhancers (SE), and that those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of RORγt. Importantly, IL-6-STAT3 signaling facilitates TRIM28 binding to the Il17-Il17f locus, and this process is required for epigenetic activation and high-order chromosomal interaction. TRIM28 also forms a complex with STAT3 and RORγt, and promotes the recruitment of RORγt to its target cytokine genes. Our study thus suggests TRIM28 to be important for the epigenetic activation during Th17 cell differentiation, and prompts the potential use of epigenetic interventions for Th17-related autoimmune diseases.

Suggested Citation

  • Yu Jiang & Ying Liu & Huiping Lu & Shao-Cong Sun & Wei Jin & Xiaohu Wang & Chen Dong, 2018. "Epigenetic activation during T helper 17 cell differentiation is mediated by Tripartite motif containing 28," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03852-2
    DOI: 10.1038/s41467-018-03852-2
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    Cited by:

    1. Wen-Lan Yang & Weinan Qiu & Ting Zhang & Kai Xu & Zi-Juan Gu & Yu Zhou & Heng-Ji Xu & Zhong-Zhou Yang & Bin Shen & Yong-Liang Zhao & Qi Zhou & Ying Yang & Wei Li & Peng-Yuan Yang & Yun-Gui Yang, 2023. "Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Ma’ayan Israeli & Yaara Finkel & Yfat Yahalom-Ronen & Nir Paran & Theodor Chitlaru & Ofir Israeli & Inbar Cohen-Gihon & Moshe Aftalion & Reut Falach & Shahar Rotem & Uri Elia & Ital Nemet & Limor Klik, 2022. "Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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