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Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation

Author

Listed:
  • Sugata Manna

    (Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Jong Kyong Kim

    (Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
    Present address: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China)

  • Catherine Baugé

    (Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health
    Present address: EA4652 Microenvironnement Cellulaire et Pathologies, UFR de médecine, Université de Caen Basse-Normandie, Caen, France)

  • Margaret Cam

    (Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yongmei Zhao

    (Leidos Biomedical Research, Frederick National Laboratory for Cancer Research)

  • Jyoti Shetty

    (Leidos Biomedical Research, Frederick National Laboratory for Cancer Research)

  • Melanie S. Vacchio

    (Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Ehydel Castro

    (Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Bao Tran

    (Leidos Biomedical Research, Frederick National Laboratory for Cancer Research)

  • Lino Tessarollo

    (Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Rémy Bosselut

    (Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

Abstract

Although histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4+ T-cell precursors. Here we show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Thymocyte expression of S1pr1 was not rescued in Jmjd3- and Utx-deficient male mice, which carry the catalytically inactive Utx homolog Uty, supporting the conclusion that it requires H3K27Me3 demethylase activity. These findings demonstrate that Jmjd3 and Utx are required for T-cell development, and point to a requirement for their H3K27Me3 demethylase activity in cell differentiation.

Suggested Citation

  • Sugata Manna & Jong Kyong Kim & Catherine Baugé & Margaret Cam & Yongmei Zhao & Jyoti Shetty & Melanie S. Vacchio & Ehydel Castro & Bao Tran & Lino Tessarollo & Rémy Bosselut, 2015. "Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9152
    DOI: 10.1038/ncomms9152
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    Cited by:

    1. Fenfen Li & Jia Jing & Miranda Movahed & Xin Cui & Qiang Cao & Rui Wu & Ziyue Chen & Liqing Yu & Yi Pan & Huidong Shi & Hang Shi & Bingzhong Xue, 2021. "Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat," Nature Communications, Nature, vol. 12(1), pages 1-22, December.

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