Genetic studies of components of the mammalian NURD complex have shed light on its functions during development. Inactivation of mouse Mbd3 results in death during mid-gestation, stemming from the failure of the inner cell mass to develop into a mature epiblast and the subsequent failure of embryonic and extra-embryonic tissues to organize properly after implantation72. Surprisingly, Mbd3-null ESCs are viable and can initiate differentiation in culture, but they fail to commit to developmental lineages, as a result of impaired silencing of pluripotency genes73. Loss of Mbd3 results in the failure to assemble NURD complexes and probably reflects a loss of function for these complexes. Hence, the NURD complex is crucial for the correct silencing of genes during early development to allow proper patterning and lineage commitment. NURD complexes are also required in later development. Conditional inactivation of Chd4 in the haematopoietic cells of mice leads to impaired haematopoietic stem-cell homeostasis and impaired differentiation into myeloid cells, and to defective thymocyte development and defective activation of the Cd4 locus74,75. Thus it seems that NURD and BAF complexes have specific, opposing, roles at the Cd4 locus.
