A newly published paper in PLoS Biology (Li et al 2008) finds that many transcription factors are non-specifiaccly bound to DNA and they may not be involved in regulating gene expression at most binding sites. For an explanation of why this shold not be a surprise see Repression of the lac Operon.
Here's the Author Summary of the paper.
One of the largest classes of regulatory proteins in animals, sequence-specific DNA binding transcription factors determine in which cells genes will be expressed and so control the development of an animal from a single cell to a morphologically complex adult. Understanding how this process is coordinated depends on knowing the number and types of genes that each transcription factor binds and regulates. Using immunoprecipitation of in vivo crosslinked chromatin coupled with DNA microarray hybridization (ChIP/chip), we have determined the genomic binding sites in early embryos of six transcription factors that play a crucial role in early development of the fruit fly Drosophila melanogaster. We find that these proteins bind to several thousand genomic regions that lie close to approximately half the protein coding genes. Although this is a much larger number of genes than these factors are generally thought to regulate, we go on to show that whereas the more highly bound genes generally look to be functional targets, many of the genes bound at lower levels do not appear to be regulated by these factors. Our conclusions differ from those of other groups who have not distinguished between different levels of DNA binding in vivo using similar assays and who have generally assumed that all detected binding is functional.
Li et al. (2008) Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm. [PLoS Biology]