Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination

Journal article


Publication Details

Author(s): Wu LMN, Wang J, Conidi A, Zhao C, Wang H, Ford Z, Zhang L, Zweier C, Ayee BG, Maurel P, Zwijsen A, Chan JR, Jankowski MP, Huylebroeck D, Lu QR
Journal: Nature Neuroscience
Publication year: 2016
Volume: 19
Journal issue: 8
Pages range: 1060-72
ISSN: 1097-6256


Abstract


The mechanisms that coordinate and balance a complex network of opposing regulators to control Schwann cell (SC) differentiation remain elusive. Here we demonstrate that zinc-finger E-box-binding homeobox 2 (Zeb2, also called Sip1) transcription factor is a critical intrinsic timer that controls the onset of SC differentiation by recruiting histone deacetylases HDAC 1 and 2 (HDAC1/2) and nucleosome remodeling and deacetylase complex (NuRD) co-repressor complexes in mice. Zeb2 deletion arrests SCs at an undifferentiated state during peripheral nerve development and inhibits remyelination after injury. Zeb2 antagonizes inhibitory effectors including Notch and Sox2. Importantly, genome-wide transcriptome analysis reveals a Zeb2 target gene encoding the Notch effector Hey2 as a potent inhibitor for Schwann cell differentiation. Strikingly, a genetic Zeb2 variant associated with Mowat-Wilson syndrome disrupts the interaction with HDAC1/2-NuRD and abolishes Zeb2 activity for SC differentiation. Therefore, Zeb2 controls SC maturation by recruiting HDAC1/2-NuRD complexes and inhibiting a Notch-Hey2 signaling axis, pointing to the critical role of HDAC1/2-NuRD activity in peripheral neuropathies caused by ZEB2 mutations.



External institutions with authors

Cincinnati Children's Hospital Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
The State University of New Jersey (Rutgers)
University of California San Francisco (UCSF)


How to cite

APA:
Wu, L.M.N., Wang, J., Conidi, A., Zhao, C., Wang, H., Ford, Z.,... Lu, Q.R. (2016). Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination. Nature Neuroscience, 19(8), 1060-72. https://dx.doi.org/10.1038/nn.4322

MLA:
Wu, Lai Man Natalie, et al. "Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination." Nature Neuroscience 19.8 (2016): 1060-72.

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Last updated on 2018-09-10 at 02:19