Our laboratory has previously demonstrated the importance of epigenetic mechanisms for activating mb-1 (Ig-α/Cd79a) promoters in B cell progenitors. In response to the transcription factors EBF1 and Pax5, mb-1 promoters undergo stepwise epigenetic remodeling prior to their transcription. This regulation includes at least two components: enhancement of chromatin accessibility and the loss of CpG methylation. These mechanisms require SWI/SNF chromatin remodeling complexes. In opposition to SWI/SNF, Mi-2/NuRD complexes provide a barrier to activation in the absence of transcriptional activators. To better understand how Mi-2/NuRD controls transcription, we developed an in vitro cell system that allows for depletion of endogenous Mi-2β(CHD4), the catalytic component of Mi-2/NuRD, concurrent with exogenous expression of wild type or mutated Mi-2β and transcriptional activators in B cells. Our data demonstrate that multiple domains in Mi-2β are required for its association with chromatin and transcriptional attenuation. Furthermore, the data suggest that Mi-2/NuRD complexes bind and stabilize DNA methylation. Knockdowns of methyl-binding proteins in Mi-2/NuRD complexes confirmed their importance for functions of Mi-2/NuRD. These data suggest a hierarchy of function in which recruitment or exclusion of chromatin remodeling complexes by transcription factors including EBF1 regulates gene expression during B cell ontogeny.