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

Composite elements are regulatory modules of promoters or enhancers that co nsist of binding sites of two different but synergizing transcription facto rs. A well-studied example is nuclear factors of activated T-cell (NFAT) si tes 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 re lative to transcription start sites; and (c) involves cluster analysis of p otential NFAT composite elements. All three steps progressively helped to d iscriminate T-cell-specific promoter sequences against other functional reg ions (coding and intronic sequences) of the same genes, against promoters o f muscle-specific genes or against random sequences. Using this approach, w e identified potential NFAT composite elements in promoters of cytokine gen es and their receptors as well as in promoters of genes for AP-1 family mem bers, Ca2+-binding proteins and some other components of the regulatory net work operating in activated T-cells and other immune cells. The method deve loped can be adapted to characterize and identify other composite elements as well. The program for recognition NFAT composite elements is available t hrough the World Wide Web (http://compel.bionet.nsc.ru/FunSite/CompelScan.h tml and http://trans-fac.gbf.de/dbsearch/funsitep/s_comp.html). (C) 1999 Ac ademic Press.