Despite the well-established fact that NuRD (nucleosome remodeling and histone deacetylase) is incapable of actively demethylating DNA, the complex is surprisingly showed to be required for the establishment of unmethylated state at promoters of ribosomal genes. But the molecular mechanism underlying how NuRD mediates unmethylation at rDNA promoters remains obscure. Here we show that NuRD directly binds to the promoter of rDNA transcription silencer TIP5 (TTF-I interacting protein 5), one of the components of nucleolar remodeling complex NoRC that silences rRNA genes by recruiting DNA methyltransferase to rDNA promoters and increasing DNA methylation. NuRD negatively regulates TIP5 expression, thereby inhibiting rDNA methylation and maintaining demethylation state of rDNA promoters. The deficiency of NuRD components in reprogrammed cells activates TIP5 expression, resulting in the increased fraction of heterochromatic rRNA genes and transcriptional silencing. Thus, NuRD is able to control methylation status of rDNA promoters through crosstalking with NoRC complex. (c) 2013 Elsevier Inc. All rights reserved.