期刊
NATURE NEUROSCIENCE
卷 14, 期 4, 页码 437-U59出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2780
关键词
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资金
- US National Institutes of Health [NS072427]
- National Multiple Sclerosis Society [RG3978]
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-kappa B, 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-kappa B 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-.B protein complex switched from associating with p300 to associating with HDAC1/2 as Schwann cells differentiated. NF-kappa B 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.
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