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Tet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development

Author

Listed:
  • Shaohai Fang

    (Texas A&M University)

  • Jia Li

    (Texas A&M University)

  • Yang Xiao

    (Texas Heart Institute, Cardiomyocyte Renewal Lab
    Baylor College of Medicine, One Baylor Plaza)

  • Minjung Lee

    (Texas A&M University)

  • Lei Guo

    (Texas A&M University)

  • Wei Han

    (Texas A&M University)

  • Tingting Li

    (Texas A&M University)

  • Matthew C. Hill

    (Baylor College of Medicine, One Baylor Plaza)

  • Tingting Hong

    (Texas A&M University)

  • William Mo

    (Texas A&M University)

  • Rang Xu

    (Shanghai Jiao Tong University)

  • Ping Zhang

    (Shanghai Jiao Tong University)

  • Fen Wang

    (Texas A&M University)

  • Jiang Chang

    (Texas A&M University)

  • Yubin Zhou

    (Texas A&M University
    Texas A&M University)

  • Deqiang Sun

    (Texas A&M University)

  • James F. Martin

    (Texas Heart Institute, Cardiomyocyte Renewal Lab
    Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine)

  • Yun Huang

    (Texas A&M University
    CPRIT Scholar in Cancer Research
    Texas A&M University)

Abstract

Tet-mediated DNA demethylation plays an important role in shaping the epigenetic landscape and chromatin accessibility to control gene expression. While several studies demonstrated pivotal roles of Tet in regulating embryonic development, little is known about their functions in heart development. Here we analyze DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice. We find that cardiac-specific deletion of Tet2 and Tet3 in mice (Tet2/3-DKO) leads to ventricular non-compaction cardiomyopathy (NCC) with embryonic lethality. Single-cell RNA-seq analyses reveal a reduction in cardiomyocyte numbers and transcriptional reprogramming in cardiac tissues upon Tet2/3 depletion. Impaired DNA demethylation and reduced chromatin accessibility in Tet2/3-DKO mice further compromised Ying-yang1 (YY1) binding to its genomic targets, and perturbed high-order chromatin organization at key genes involved in heart development. Our studies provide evidence of the physiological role of Tet in regulating DNA methylation dynamics and chromatin organization during early heart development.

Suggested Citation

  • Shaohai Fang & Jia Li & Yang Xiao & Minjung Lee & Lei Guo & Wei Han & Tingting Li & Matthew C. Hill & Tingting Hong & William Mo & Rang Xu & Ping Zhang & Fen Wang & Jiang Chang & Yubin Zhou & Deqiang , 2019. "Tet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12325-z
    DOI: 10.1038/s41467-019-12325-z
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    Cited by:

    1. Jianfang Li & Xinwei Wu & Jie Ke & Minjung Lee & Qingping Lan & Jia Li & Jianxiu Yu & Yun Huang & De-Qiang Sun & Ruiyu Xie, 2022. "TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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