HDAC-mediated Deacetylation of NF-κB is Critical for Schwann cell Myelination

Schwann cell myelination is tightly regulated by timely expression of key transcriptional regulators that respond to specific environmental cues, yet molecular mechanisms underlying such a process are poorly understood. Here, we report that HDAC1/2-regulated acetylation state of NF-κB is critical in orchestrating the myelination program. Mice lacking HDAC1/2 exhibit severe dysmyelination with Schwann cell development arrested at the immature stage. We find that NF-κB p65 becomes heavily acetylated in HDAC1/2 mutants, inhibiting the expression of positive regulators of myelination, while inducing the expression of differentiation inhibitors. We observe that NF-κB protein complex switches its association with p300 to that with HDAC1/2 as Schwann cells differentiate. NF-κB and HDAC1/2 act coordinately 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