Transcriptional regulation of interleukin 3 gene expression in T lymphocytes.
Interleukin 3 (IL-3 or multi-colony-stimulating factor) plays an important role in the hematopoietic response to inflammatory stimuli through its action on both immature and mature blood cells. Like other lymphokines, IL-3 is produced in response to activation of the T-cell receptor and protein kinase C pathways. By using nuclear run-on assays of quiescent and stimulated T-cell lines, we demonstrate that IL-3 gene expression is controlled, at least in part, at the level of transcription. Functional reporter gene analysis was used to delineate two regions of the IL-3 5' flanking sequence responsible for transcriptional stimulation. DNA binding proteins that potentially mediate these responses were then recognized by mobility-shift and DNase footprinting assays. One region responsible for transcriptional enhancement was localized to the sequence GATGAATAAT, the cognate site of a transcription factor, here termed NF-IL3-A. A second region of functional activity and protein binding was localized to a single transcription factor AP-1 site. In addition three functionally inhibitory regions were identified. These results, along with the further characterization of NF-IL3-A, will contribute to the understanding of IL-3 gene regulation in stimulated T cells.
Shoemaker
S G
SG
Department of Medicine, University of Washington, Seattle 98195.
Hromas
R
R
Kaushansky
K
K
D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009710:Nucleotide Mapping; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D007377:Interleukin-3; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012334:RNA, Neoplasm