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Nucleoprotein structure of the CD4 locus: implications for the mechanisms underlying CD4 regulation during T cell development.


ABSTRACT: The CD4 gene is regulated in a stage-specific manner during T cell development, being repressed in CD4(-)CD8(-) double-negative (DN) and CD8 cells, but expressed in CD4(+)CD8(+) double-positive (DP) and CD4 cells. Furthermore, the expression/repression pattern is reversible in developing (DN and DP) thymocytes, but irreversible in mature (CD4 and CD8) T cells. Here, we explored the molecular mechanisms underlying this complex mode of regulation by examining the nucleoprotein structure of the CD4 locus throughout T cell development and in DN cells lacking the CD4 silencer. In DN cells, the CD4 enhancer is preloaded with multiple transcription activators, but p300 recruitment is impaired by the silencer that is associated with the repressor Runx1. DP cells achieve high-level CD4 expression v

SUBMITTER: Yu M 

PROVIDER: S-EPMC2268827 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature