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Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers

Author

Listed:
  • Delong Feng

    (Southern Medical University)

  • Yanhong Chen

    (People’s Hospital of Zhengzhou University, Zhengzhou university)

  • Ranran Dai

    (Southern Medical University)

  • Shasha Bian

    (People’s Hospital of Zhengzhou University, Zhengzhou university)

  • Wei Xue

    (Southern Medical University)

  • Yongchang Zhu

    (People’s Hospital of Zhengzhou University, Zhengzhou university)

  • Zhaoqiang Li

    (Southern Medical University)

  • Yiting Yang

    (Southern Medical University)

  • Yan Zhang

    (Southern Medical University)

  • Jiarui Zhang

    (Southern Medical University)

  • Jie Bai

    (People’s Hospital of Zhengzhou University, Zhengzhou university)

  • Litao Qin

    (People’s Hospital of Zhengzhou University, Zhengzhou university)

  • Yoshinori Kohwi

    (University of California, San Francisco)

  • Weili Shi

    (People’s Hospital of Zhengzhou University, Zhengzhou university)

  • Terumi Kohwi-Shigematsu

    (University of California, San Francisco)

  • Jing Ma

    (Fudan University)

  • Shixiu Liao

    (People’s Hospital of Zhengzhou University, Zhengzhou university
    People’s Hospital of Henan University, Henan University)

  • Bingtao Hao

    (Southern Medical University)

Abstract

CD4+ and CD8+ double-positive (DP) thymocytes play a crucial role in T cell development in the thymus. DP cells rearrange the T cell receptor gene Tcra to generate T cell receptors with TCRβ. DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, regulatory T cells, or invariant nature kill T cells (iNKT) in response to TCR signaling. Chromatin organizer SATB1 is highly expressed in DP cells and is essential in regulating Tcra rearrangement and differentiation of DP cells. Here we explored the mechanism of SATB1 orchestrating gene expression in DP cells. Single-cell RNA sequencing shows that Satb1 deletion changes the cell identity of DP thymocytes and down-regulates genes specifically and highly expressed in DP cells. Super-enhancers regulate the expressions of DP-specific genes, and our Hi-C data show that SATB1 deficiency in thymocytes reduces super-enhancer activity by specifically decreasing interactions among super-enhancers and between super-enhancers and promoters. Our results reveal that SATB1 plays a critical role in thymocyte development to promote the establishment of DP cell identity by globally regulating super-enhancers of DP cells at the chromatin architectural level.

Suggested Citation

  • Delong Feng & Yanhong Chen & Ranran Dai & Shasha Bian & Wei Xue & Yongchang Zhu & Zhaoqiang Li & Yiting Yang & Yan Zhang & Jiarui Zhang & Jie Bai & Litao Qin & Yoshinori Kohwi & Weili Shi & Terumi Koh, 2022. "Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33333-6
    DOI: 10.1038/s41467-022-33333-6
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    Cited by:

    1. Motoi Yamashita & Chihiro Ogawa & Baihao Zhang & Tetsuro Kobayashi & Aneela Nomura & Clive Barker & Chengcheng Zou & Satoshi Yamanaka & Ken-ichiro Hayashi & Yoichi Shinkai & Kazuyo Moro & Sidonia Farg, 2024. "Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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