HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination

Ying Chen, Haibo Wang, Sung Ok Yoon, Xiaomei Xu, Michael O. Hottiger, John Svaren, Klaus A. Nave, Haesun A. Kim, Eric N. Olson, Q. Richard Lu

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117 Scopus citations

Abstract

Schwann cell myelination is tightly regulated by timely expression of key transcriptional regulators that respond to specific environmental cues, but the molecular mechanisms underlying such a process are poorly understood. We found that the acetylation state of NF-κwhich is regulated by histone deacetylases (HDACs) 1 and 2, is critical for orchestrating the myelination program. Mice lacking both HDACs 1 and 2 (HDAC1/2) exhibited severe myelin deficiency with Schwann cell development arrested at the immature stage. NFκ p65 became heavily acetylated in HDAC1/2 mutants, inhibiting the expression of positive regulators of myelination and inducing the expression of differentiation inhibitors. We observed that the NF-κb protein complex switched from associating with p300 to associating with HDAC1/2 as Schwann cells differentiated. NF-κb and HDAC1/2 acted in a coordinated fashion to regulate the transcriptionally linked chromatin state for Schwann cell myelination. Thus, our results reveal an HDAC-mediated developmental switch for controlling myelination in the peripheral nervous system.

Original languageEnglish (US)
Pages (from-to)437-441
Number of pages5
JournalNature neuroscience
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2011

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Chen, Y., Wang, H., Yoon, S. O., Xu, X., Hottiger, M. O., Svaren, J., Nave, K. A., Kim, H. A., Olson, E. N., & Lu, Q. R. (2011). HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination. Nature neuroscience, 14(4), 437-441. https://doi.org/10.1038/nn.2780