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CTCF-mediated chromatin looping in EGR2 regulation and SUZ12 recruitment critical for peripheral myelination and repair

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  • Jincheng Wang

    (Zhejiang University)

  • Jiajia Wang

    (Cincinnati Children’s Hospital Medical Center)

  • Lijun Yang

    (Cincinnati Children’s Hospital Medical Center)

  • Chuntao Zhao

    (Cincinnati Children’s Hospital Medical Center)

  • Laiman Natalie Wu

    (Cincinnati Children’s Hospital Medical Center)

  • Lingli Xu

    (Cincinnati Children’s Hospital Medical Center)

  • Feng Zhang

    (Cincinnati Children’s Hospital Medical Center)

  • Qinjie Weng

    (Zhejiang University)

  • Michael Wegner

    (Friedrich-Alexander-Universität Erlangen-Nürnberg)

  • Q. Richard Lu

    (Cincinnati Children’s Hospital Medical Center)

Abstract

Chromatin organization is critical for cell growth, differentiation, and disease development, however, its functions in peripheral myelination and myelin repair remain elusive. In this report, we demonstrate that the CCCTC-binding factor (CTCF), a crucial chromatin organizer, is essential for Schwann cell myelination and myelin regeneration after nerve injury. Inhibition of CTCF or its deletion blocks Schwann cell differentiation at the pro-myelinating stage, whereas overexpression of CTCF promotes the myelination program. We find that CTCF establishes chromatin interaction loops between enhancer and promoter regulatory elements and promotes expression of a key pro-myelinogenic factor EGR2. In addition, CTCF interacts with SUZ12, a component of polycomb-repressive-complex 2 (PRC2), to repress the transcriptional program associated with negative regulation of Schwann cell maturation. Together, our findings reveal a dual role of CTCF-dependent chromatin organization in promoting myelinogenic programs and recruiting chromatin-repressive complexes to block Schwann cell differentiation inhibitors to control peripheral myelination and repair.

Suggested Citation

  • Jincheng Wang & Jiajia Wang & Lijun Yang & Chuntao Zhao & Laiman Natalie Wu & Lingli Xu & Feng Zhang & Qinjie Weng & Michael Wegner & Q. Richard Lu, 2020. "CTCF-mediated chromatin looping in EGR2 regulation and SUZ12 recruitment critical for peripheral myelination and repair," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17955-2
    DOI: 10.1038/s41467-020-17955-2
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    Cited by:

    1. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Thomas F. Barrett & Bhuvic Patel & Saad M. Khan & Riley D. Z. Mullins & Aldrin K. Y. Yim & Sangami Pugazenthi & Tatenda Mahlokozera & Gregory J. Zipfel & Jacques A. Herzog & Michael R. Chicoine & Came, 2024. "Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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