A histone methyltransferase ESET is critical for T cell development

Shoichi Takikita, Ryunosuke Muro, Toshiyuki Takai, Takeshi Otsubo, Yuki I. Kawamura, Taeko Dohi, Hiroyo Oda, Masayuki Kitajima, Kenshiro Oshima, Masahira Hattori, Takaho A. Endo, Tetsuro Toyoda, John Weis, Yoichi Shinkai, Harumi Suzuki

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    ESET/SETDB1, one of the major histone methyltransferases, catalyzes histone 3 lysine 9 (H3K9) trimethylation. ESET is critical for suppressing expression of retroviral elements in embryonic stem cells; however, its role in the immune system is not known.We found that thymocyte-specific deletion of ESET caused impaired T cell development, with CD8 lineage cells being most severely affected. Increased apoptosis of CD8 single-positive cells was observed, and TCR-induced ERK activation was severely inhibited in ESET2/2 thymocytes. Genome-wide comprehensive analysis of mRNA expression and H3K9 trimethylation revealed that ESET regulates expression of numerous genes in thymocytes. Among them, FcgRIIB, whose signaling can inhibit ERK activation, was strongly and ectopically expressed in ESET2/2 thymocytes. Indeed, genetic depletion of FcgRIIB in ESET2/2 thymocytes rescued impaired ERK activation and partially restored defective positive selection in ESET2/2 mice. Therefore, impaired T cell development in ESET2/2 mice is partly due to the aberrant expression of FcgRIIB. Collectively, to our knowledge, we identify ESET as the first trimethylated H3K9 histone methyltransferase playing a crucial role in T cell development.

    Original languageEnglish
    Pages (from-to)2269-2279
    Number of pages11
    JournalJournal of Immunology
    Volume197
    Issue number6
    DOIs
    Publication statusPublished - 2016 Sep 15

    Fingerprint

    Thymocytes
    T-Lymphocytes
    Embryonic Stem Cells
    Histones
    Lysine
    Immune System
    histone methyltransferase
    Genome
    Apoptosis
    Gene Expression
    Messenger RNA

    ASJC Scopus subject areas

    • Immunology

    Cite this

    Takikita, S., Muro, R., Takai, T., Otsubo, T., Kawamura, Y. I., Dohi, T., ... Suzuki, H. (2016). A histone methyltransferase ESET is critical for T cell development. Journal of Immunology, 197(6), 2269-2279. https://doi.org/10.4049/jimmunol.1502486

    A histone methyltransferase ESET is critical for T cell development. / Takikita, Shoichi; Muro, Ryunosuke; Takai, Toshiyuki; Otsubo, Takeshi; Kawamura, Yuki I.; Dohi, Taeko; Oda, Hiroyo; Kitajima, Masayuki; Oshima, Kenshiro; Hattori, Masahira; Endo, Takaho A.; Toyoda, Tetsuro; Weis, John; Shinkai, Yoichi; Suzuki, Harumi.

    In: Journal of Immunology, Vol. 197, No. 6, 15.09.2016, p. 2269-2279.

    Research output: Contribution to journalArticle

    Takikita, S, Muro, R, Takai, T, Otsubo, T, Kawamura, YI, Dohi, T, Oda, H, Kitajima, M, Oshima, K, Hattori, M, Endo, TA, Toyoda, T, Weis, J, Shinkai, Y & Suzuki, H 2016, 'A histone methyltransferase ESET is critical for T cell development' Journal of Immunology, vol. 197, no. 6, pp. 2269-2279. https://doi.org/10.4049/jimmunol.1502486
    Takikita S, Muro R, Takai T, Otsubo T, Kawamura YI, Dohi T et al. A histone methyltransferase ESET is critical for T cell development. Journal of Immunology. 2016 Sep 15;197(6):2269-2279. https://doi.org/10.4049/jimmunol.1502486
    Takikita, Shoichi ; Muro, Ryunosuke ; Takai, Toshiyuki ; Otsubo, Takeshi ; Kawamura, Yuki I. ; Dohi, Taeko ; Oda, Hiroyo ; Kitajima, Masayuki ; Oshima, Kenshiro ; Hattori, Masahira ; Endo, Takaho A. ; Toyoda, Tetsuro ; Weis, John ; Shinkai, Yoichi ; Suzuki, Harumi. / A histone methyltransferase ESET is critical for T cell development. In: Journal of Immunology. 2016 ; Vol. 197, No. 6. pp. 2269-2279.
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    abstract = "ESET/SETDB1, one of the major histone methyltransferases, catalyzes histone 3 lysine 9 (H3K9) trimethylation. ESET is critical for suppressing expression of retroviral elements in embryonic stem cells; however, its role in the immune system is not known.We found that thymocyte-specific deletion of ESET caused impaired T cell development, with CD8 lineage cells being most severely affected. Increased apoptosis of CD8 single-positive cells was observed, and TCR-induced ERK activation was severely inhibited in ESET2/2 thymocytes. Genome-wide comprehensive analysis of mRNA expression and H3K9 trimethylation revealed that ESET regulates expression of numerous genes in thymocytes. Among them, FcgRIIB, whose signaling can inhibit ERK activation, was strongly and ectopically expressed in ESET2/2 thymocytes. Indeed, genetic depletion of FcgRIIB in ESET2/2 thymocytes rescued impaired ERK activation and partially restored defective positive selection in ESET2/2 mice. Therefore, impaired T cell development in ESET2/2 mice is partly due to the aberrant expression of FcgRIIB. Collectively, to our knowledge, we identify ESET as the first trimethylated H3K9 histone methyltransferase playing a crucial role in T cell development.",
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    AU - Kawamura, Yuki I.

    AU - Dohi, Taeko

    AU - Oda, Hiroyo

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    AU - Hattori, Masahira

    AU - Endo, Takaho A.

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