Gerald Siu | PubMed Health

PubMed2003

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.

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PubMed2002

Controlling CD4 gene expression during T cell lineage commitment.

T cell lineage commitment as the double-positive (DP) thymocyte matures into the single-positive (SP) T cell requires the irreversible repression or maintenance of CD4 gene expression. Signals transmitted from the T cell antigen receptor (TCR) during thymic selection are believed to be linked to the transcriptional regulation of the CD4 gene; thus, a study of the factors that control CD4 gene expression may lead to further insight into the molecular mechanisms that drive T cell development. This review discusses the work conducted to date to identify and characterize the transcriptional control elements in the CD4 locus and the factors that mediate their function. From these studies, it is clear that the molecular mechanisms controlling CD4 gene expression are very complex and are controlled by many different signals as the thymocyte develops.

Animals↗