HDAC-mediated deacetylation of NF-?B 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-?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-?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-?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.

SUBMITTER: Chen Y 

PROVIDER: S-EPMC3074381 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature