Most transcription factor binding sites are in a few mosaic classes of the human genome

Many algorithms for finding transcription factor binding sites have concentrated on the characterisation of the binding site itself: and these algorithms lead to a large number of false positive sites. The DNA sequence which does not bind has been modeled only to the extent necessary to complement this formulation.

We find that the human genome may be described by 19 pairs of mosaic classes, each defined by its base frequencies, (or more precisely by the frequencies of doublets), so that typically a run of 10 to 100 bases belongs to the same class. Most experimentally verified binding sites are in the same four pairs of classes. In our sample of seventeen transcription factors - taken from different families of transcription factors - the average proportion of sites in this subset of classes was 75%, with values for individual factors ranging from 48% to 98%. By contrast these same classes contain only 26% of the bases of the genome and only 31% of occurrences of the motifs of these factors - that is places where one might expect the factors to bind. These results are not a consequence of the class composition in promoter regions.

This method of analysis will help to find transcription factor binding sites and assist with the problem of false positives. These results also imply a profound difference between the mosaic classes.