Transcription factors (TFs) regulate gene expression by recognizing and binding to specific regulatory regions on the genome, which in higher eukaryotes can occur far away from the regulated genes. Recently, Affymetrix developed the high-density oligonucleotide arrays that tile all the non-repetitive sequences of the human genome at 35 bp resolution. This new array platform allows for the unbiased mapping of in vivo TF binding sequences (TFBSs) using Chromatin ImmunoPrecipitation followed by microarray experiments (ChIP-chip). The massive dataset generated from these experiments pose great challenges for data analysis.