Mi-2/nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complexes 
are important regulators of chromatin structure and DNA accessibility. We 
examined requirements for individual domains of chromodomain helicase 
DNA-binding protein 4 (CHD4), a core catalytic component of NuRD complexes, as 
well as the NuRD subunit methyl-binding domain protein 2 (MBD2) and methylated 
DNA, for NuRD function in the context of tissue-specific transcription. By 
itself, loss of NuRD activity is not sufficient for transcriptional activation. 
However, NuRD complexes greatly reduce activation of the B cell-specific mb-1 
(Cd79a) gene by the transcription factors EBF1 and Pax5. Using our B cell model 
system, we determined that the two chromodomains and ATPase/helicase and 
C-terminal domains (CTD) of CHD4 are all necessary for repression of mb-1 
promoters by NuRD. All of these domains except the CTD are required for 
efficient association of CHD4 with mb-1 promoter chromatin. Loss of MBD2 
expression or of DNA methylation impaired association of CHD4 with mb-1 promoter 
chromatin and enhanced its transcription. We conclude that repressive functions 
of MBD2-containing NuRD complexes are dependent on cooperative interactions 
between the major domains of CHD4 with histones and DNA and on binding of 
methylated DNA by MBD2.