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 expressed 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 within the first 24 h after T-cell activation. The second site binds an apparently novel complex that is upregulated later, between days 3 and 5. These data provide an explanation for the immediate-early expression of RANTES in some cell types and identify apparently novel factors contributing to late RANTES transcription in T cells. The results reveal a developmental switch occurring during normal T-cell maturation coincident with the onset of terminal differentiation and the binding of late-acting factors to sequences of the RANTES promoter.
Multidisciplinary Program in Immunology, Stanford University School of Medicine, California 94305-5119, USA.
B D
BD
Ortiz
A M
AM
Krensky
P J
PJ
Nelson
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D018946:Chemokine CCL5; D014157:Transcription Factors; D004247:DNA