Recognition of NFATp/AP-1 composite elements within genes induced upon the activation of immune cells

• Published in: Journal of molecular biology Vol. 288; no. 3; pp. 353 - 376
• Main Authors: Kel, Alexander, Kel-Margoulis, Olga, Babenko, Vladimir, Wingender, Edgar
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.05.1999
• Subjects: Animals; Base Sequence; Binding Sites; composite elements; computer-assisted prediction; DNA; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Gene Expression; Humans; immune response; Lymphocyte Activation - genetics; Lymphokines - genetics; Mice; Molecular Sequence Data; NFATC Transcription Factors; NFATp/ AP-1; Nuclear Proteins; Promoter Regions, Genetic; Sequence Homology, Nucleic Acid; T-Lymphocytes - immunology; Transcription Factor AP-1 - chemistry; Transcription Factor AP-1 - metabolism; Transcription Factors - chemistry; Transcription Factors - metabolism; CE; computer-assisted prediction; IL; COMPEL; EST; PWM; composite elements; PKC; MHC; AP-1; NFAT; CS; TF; immune response; GM-CSF; TRRD; EPD; NFATp/ AP-1; TRANSFAC
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1999.2684

Composite elements are regulatory modules of promoters or enhancers that consist of binding sites of two different but synergizing transcription factors. A well-studied example is nuclear factors of activated T-cell (NFAT) sites which are composite elements of a NFATp/c and an activating protein 1 (AP-1) binding site. We have developed a computational approach to identify potential NFAT target genes which (a) comprises an improved method to scan for individual NFAT composite elements; (b) considers positional effects relative to transcription start sites; and (c) involves cluster analysis of potential NFAT composite elements. All three steps progressively helpX?ed to discriminate T-cell-specific promoter sequences against other functional regions (coding and intronic sequences) of the same genes, against promoters of muscle-specific genes or against random sequences. Using this approach, we identified potential NFAT composite elements in promoters of cytokine genes and their receptors as well as in promoters of genes for AP-1 family members, Ca 2+-binding proteins and some other components of the regulatory network operating in activated T-cells and other immune cells. The method developed can be adapted to characterize and identify other composite elements as well. The program for recognition NFAT composite elements is available through the World Wide Web ( http://compel.bionet.nsc.ru/FunSite/CompelScan.html and http://transfac.gbf.de/dbsearch/funsitep/s_comp.html).