sufficiently high concentrations in cells such that they can occupy their recognition sequences in highly accessible chromatin without the aid of physical cooperative interactions with other proteins, leading to highly overlapping, graded binding of unrelated factors. Background In vivo crosslinking studies show that a wide range of animal transcription factors each bind to many thousands of DNA regions throughout the genome and that not all of this binding is necessarily functional (for example, [ 1 - 19 ]). For example, our studies of over 20 transcriptional regulators in the Drosophila blastoderm embryo show that the few hundred most highly bound DNA regions include all of these proteins' known target cis -regulatory modules (CRMs) and are preferentially associated with developmental control genes and genes whose expression is strongly patterned in the blastoderm [ 1 - 3 , 14 , 17 , 19 ]. In contrast, the thousands of more poorly bound regions are preferentially associated with genes not transcribed in the early embryo and/or housekeeping genes, and are frequently present in poorly conserved non-coding DNA or in protein coding sequences. In addition, there is a surprisingly high overlap in the genomic regions bound by biochemically and functionally unrelated animal transcription factors in vivo [ 3 , 17 , 20 ], with the distinct biological specificities of factors being determined by quantitative differences in their occupancy on these shared regions [ 3 , 17 , 21 , 22 ]. What biochemical mechanisms could be responsible for these widespread, overlapping patterns of animal