KINETICS OF TRANSCRIPTION FACTORS REGULATING THE RANTES CHEMOKINE GENE REVEAL A DEVELOPMENTAL SWITCH IN NUCLEAR EVENTS DURING T-LYMPHOCYTE MATURATION

RANTES is a chemoattractant cytokine (chemokine) whose gene is express ed immediately after stimulation of several cell types but upregulated late (3 to 5 days) after activation in normal T lymphocytes. Here we describe two cis-acting elements in the human RANTES promoter that act in T lymphocytes. One site interacts with NFIL6, which is activated w ithin the first 24 h after T-cell activation. The second site binds an apparently novel complex that is upregulated later, between days 3 an d 5. These data provide an explanation for the immediate-early express ion of RANTES in some cell types and identify apparently novel factors contributing to late RANTES transcription in T cells. The results rev eal a developmental switch occurring during normal T-cell maturation c oincident with the onset of terminal differentiation and the binding o f late-acting factors to sequences of the RANTES promoter.