Hdac-mediated deacetylation of nf-κb is critical for schwann cell myelination

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-κB, which 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. NF-κB 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. Access

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SIMILAR CONTENT BEING VIEWED BY OTHERS CTCF-MEDIATED CHROMATIN LOOPING IN EGR2 REGULATION AND SUZ12 RECRUITMENT CRITICAL FOR PERIPHERAL MYELINATION AND REPAIR Article Open access 17 August

2020 HYPOXIA-INDUCED CONVERSION OF SENSORY SCHWANN CELLS INTO REPAIR CELLS IS REGULATED BY HDAC8 Article Open access 09 January 2025 PROHIBITIN 1 IS ESSENTIAL TO PRESERVE MITOCHONDRIA AND

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Chan for critical comments, and P. Casaccia for initial discussions. We thank Q. Weng and Z. Ma for technical support, O. Nakagawa and J. Chen for the p300/CBP and p65/RelA expression

vectors, and R. Kageyama for the Hes5 luciferase reporter. This study was funded in part by grants from the US National Institutes of Health (NS072427) and the National Multiple Sclerosis

Society (RG3978) to Q.R.L. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve

Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas, USA Ying Chen, Haibo Wang, Xiaomei Xu & Q Richard Lu * Molecular Biology, University of Texas

Southwestern Medical Center, Dallas, Texas, USA Ying Chen, Eric N Olson & Q Richard Lu * Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, Ohio State

University, Columbus, Ohio, USA Sung Ok Yoon * Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland Michael O Hottiger * Department of

Comparative Biosciences and the Waisman Center, University of Wisconsin, Madison, Wisconsin, USA John Svaren * Department of Neurogenetics, Max Planck Institute of Experimental Medicine,

Goettingen, Germany Klaus A Nave * Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA Haesun A Kim Authors * Ying Chen View author publications You can also

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Scholar CONTRIBUTIONS Y.C. conducted the majority of the experiments and analyzed the data. H.W. and X.X. contributed to HDAC mutant generation, phenotype analysis and biochemical assays.

S.O.K., J.S. and H.A.S. provided reagents and input. M.H. provided the p65 mutant–expression vectors. K.A.N. provided CNP-Cre mice for initial phenotype observation. E.N.O. provided

_loxP_-flanked HDAC1 and HDAC2 mice and inputs. Q.R.L. supervised the project, analyzed the data and wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Q Richard Lu. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–6 (PDF 1400 kb) RIGHTS

AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Chen, Y., Wang, H., Yoon, S. _et al._ HDAC-mediated deacetylation of NF-κB is critical for Schwann cell

myelination. _Nat Neurosci_ 14, 437–441 (2011). https://doi.org/10.1038/nn.2780 Download citation * Received: 12 November 2010 * Accepted: 18 February 2011 * Published: 20 March 2011 * Issue

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