Multicellular organisms establish and maintain different transcriptional states in disparate cell types through complex and specific regulation of gene expression. This regulation is mediated by the cooperative binding of transcription factors (TFs) to regulatory elements through the recognition of specific DNA sequence motifs. Additionally, the physical access of TFs to DNA can be modulated by epigenetic regulation, such as DNA methylation, nucleosome positioning and histone modifications. Failure to maintain this tight regulation of gene expression results in developmental defects and various diseases including cancer. We use both computational and experimental approaches and integrate genomic data to study TF binding and its regulation in cellular systems.