Composite Score

A method called 'composite score' was developed for revealing NFAT/AP-1 CEs (Kel et al., 1999). It includes two matrices, for two corresponding TFs. The range of allowed distances between matrix matches and their mutual orientation are taken into account, as well as the coordinate variation ofthe matrix scores for the two factors. A low score of one matrix is compensated by a high score of another matrix, thus providing optimal binding energy for the protein-DNA complex on the CE.

A set of 13 NFAT/AP-1 CEs was extracted from the COMPEL database (release 2.1). For each CE we used the Matchâ„¢ program and computed two scores: qNFATand qAP-1 for the two corresponding binding sites constituting the CE. From these scores two parameters, rcNFAT = log(1 - qNFAT) and rcAP-1 = log(1 - qAP-1), were calculated, estimating the binding energy for these two factors with their binding sites. To model the synergistic binding of two factors to DNA, we combined two parameters: tcNFATp and tcap-1 and designed a method for recognition of CEs. For combining these two parameters into one recognition function, we used the SITEVIDEO software (Kel et al., 1993), which provides a means of obtaining the best discrimination between a training set of CEs and control data (random sequences).

We found that identifying composite elements with this method is very effective for predicting gene-expression patterns, as demonstrated for promoters of genes

Fig. 12.5 Frequencies of NFAT/AP-1 composite elements (qCE>10.0) in the functional parts of immune cell-specific genes and muscle-specific genes and in random sequences.

highly induced upon immune response. NFAT/AP-1 composite elements were found in high concentration in the promoters of genes that are induced upon immune cell activation. (Figure 12.5).

Clusters of these composite elements provide a good landmark for identifying promoters of immune-specific genes. Several genes potentially regulated by this mechanism were revealed by genome search and suggested for experimental verification (Kel etal., 1999).

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