Several key transcription factors and coregulators important to peripheral nerve 
myelination have been identified, but the contributions of specific chromatin 
remodeling complexes to peripheral nerve myelination have not been analyzed. 
Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit 
of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling 
complex. Previous studies have shown Chd4 interacts with Nab 
(NGFI-A/Egr-binding) corepressors, which are required for early growth response 
2 (Egr2/Krox20), to direct peripheral nerve myelination by Schwann cells. In 
this study, we examined the developmental importance of the NuRD complex in 
peripheral nerve myelination through the generation of conditional Chd4 
knock-out mice in Schwann cells (Chd4(loxP/loxP); P0-cre). Chd4 conditional null 
mice were found to have delayed myelination, radial sorting defects, 
hypomyelination, and the persistence of promyelinating Schwann cells. Loss of 
Chd4 leads to elevated expression of immature Schwann cell genes (Id2, c-Jun, 
and p75), and sustained expression of the promyelinating Schwann cell gene, 
Oct6/Scip, without affecting the levels of Egr2/Krox20. Furthermore, Schwann 
cell proliferation is upregulated in Chd4-null sciatic nerve. In vivo chromatin 
immunoprecipitation studies reveal recruitment of Chd4 and another NuRD 
component, Mta2, to genes that are positively and negatively regulated by Egr2 
during myelination. Together, these results underscore the necessity of Chd4 
function to guide proper terminal differentiation of Schwann cells and implicate 
the NuRD chromatin remodeling complex as a requisite factor in timely and stable 
peripheral nerve myelination.