A conserved motif in the promoters of several cytokines expressed by human Th2-type lymphocytes.
We have recently found a novel conserved motif in the promoters of several T-cell-expressed cytokines [human interleukin-2, -4, -5 and -13 and human and mouse granulocyte/macrophage-colony stimulating factor (GM-CSF)]. It contains a core sequence CTTGG ... CCAAG which is present as part of larger palindromic sequences in each gene. This suggest that they may interact with a new family of trans-acting factors. In transfection assays, the human GM-CSF element has a strong positive effect on the expression of a reporter gene by the human T cell line Jurkat J6 upon stimulation. In DNA mobility shift assays, this sequence can give either six different specific bands which are competed out by different parts of the sequence or one specific band which is competed out by each of the inverted repeats, depending on the reconstitution conditions. In different genes, the core sequences are separated by integer numbers of helical turns. Considering the strong positive regulatory effect of this element and its presence in several T-cell-expressed cytokine genes, it may be crucial to the coordinated expression of these cytokines in T helper cells.
Staynov
D Z
DZ
Department of Allergy and Respiratory Medicine, UMDS, Guy's Hospital, University of London, UK.
Cousins
D J
DJ
Lee
T H
TH
D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D016384:Consensus Sequence; D016207:Cytokines / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D017930:Genes, Reporter; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D018418:Th2 Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor