PROJECT SUMMARY The generation of B and T lymphocytes follows their progression from uncommitted progenitors through a series of defined stages of development. At each stage, cells express a distinct set of genes, or transcriptome. These patterns of gene expression are controlled, in part, by tissue- and stage-specific epigenetic factors that limit the accessibility of chromatin. We have demonstrated that Nucleosome Remodeling and Deacetylase (NuRD) complexes, which include the Chromodomain Helicase and DNA binding 3 (CHD3; also known as Mi-2α) or the related protein CHD4 (Mi-2β) proteins, are gatekeepers of gene transcription. CHD4 has been studied extensively in B and T cells, while very little is known concerning its closely related paralog CHD3. The literature suggests that normal lymphocyte development likely requires both CHD proteins due to their distinct functions, but this has not been proven in an in vivo model system. Here, we will generate gene-targeted mice for the conditional knockout of Chd3 genes in lymphocytes of mice. These mice are currently unavailable commercially and from other research laboratories. Thus, we will generate a valuable resource that can be shared with other investigators with interests in lymphocyte development, epigenetics, and specific functions of NuRD complexes.