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- Title
ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter.
- Authors
Thomas, Ross S; Tymms, Martin J; McKinlay, Leigh H; Shannon, M Frances; Seth, Arun; Kola, Ismarl
- Abstract
Activation of helper T cells results in coordinate expression of a number of cytokines involved in differentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony stimulating factor (GM – CSF) is one such cytokine, whose increased expression results mostly from increases in transcription. Cis-acting elements with NFκB, AP1 and ETS-like binding motifs have been identified in the promoter region of the GM – CSF gene, and are important or essential for transcriptional activity following T cell activation. ETS1 is a transcription factor of the ETS family that is expressed in T cells. We have previously shown that ETS1 can transactivate GM – CSF in Jurkat T cells, but only after the cells have been stimulated by treatment with PMA and ionomycin, agents that mimic T cell activation. Thus we proposed that ETS1, which is expressed constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible factors. Here we show that ETS1 can transactivate a GM – CSF reporter construct in unstimulated Jurkat cells, providing that either NFκB or AP1 transcription factors are supplied by co-transfection. We confirm that binding of endogenous NFκB and AP1 is induced following PMA/ionomycin treatment of T cells. Transactivation by ETS1, NFκB and AP1 is synergistic, and mutation of the individual binding sites reveals that the transcriptional activities of these factors are inter-dependent. Our results suggest that constitutive ETS1, and inducible NFκB and AP1, cooperate as part of a higher order transcriptional complex in activated T cells.
- Subjects
GRANULOCYTE-macrophage colony-stimulating factor; GENES; T cells
- Publication
Oncogene, 1997, Vol 14, Issue 23, p2845
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1201125