Hierarchical interactions control CD4 gene expression during thymocyte development

CD4 gene regulation provides an ideal model for understanding the molecular events that drive T cell development. In this paper we use a transgenic approach to identify a CD4 LCR containing a stage-specific thymocyte enhancer (TE) and a region that protects against position effect variegation. Surprisingly, the TE acts indirectly through the previously defined proximal enhancer and is strongly induced upon commitment to the T cell lineage. We also describe a complex series of hierarchical control element interactions that orchestrate CD4 expression throughout thymopoiesis. These data provide a framework for understanding how CD4 gene expression is regulated in response to lineage commitment decisions.