To initiate the process of gene regulation, sequence-specific DNA-binding proteins recognize short, degenerate DNA motifs that often occur thousands of times throughout the genome. It thus appears that information provided by the linear DNA sequence alone is not
sufficient to guide DNA-binding proteins to the appropriate loci. In eukaryotic genomes, often combinations of motifs occur as clusters,
forming regulatory modules. High-resolution mapping of in-vivo nucleosome occupancy experiments indicate that nucleosome positioning
provides a source of additional information by regulating access to the DNA template. DNA-encoded positioning signals are relatively weak and difficult to detect in any individual nucleosomal sequence, and at the same time are necessarily correlated since the placement of one nucleosome imposes restrictions on others in the neighborhood. We discuss the statistical issues and challenges involved in moving beyond linear sequence-based information for improving motif discovery methods.
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