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

Jincheng Wang, Jiajia Wang, Lijun Yang, Chuntao Zhao, Laiman Natalie Wu, Lingli Xu, Feng Zhang, Qinjie Weng (), Michael Wegner and Q. Richard Lu ()
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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

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17955-2

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