Nowadays, chromatin immunoprecipitation followed by next-generation sequencing, often referred to as ChIP-Seq, has become an industry standard to study a landscape of DNA-protein interactions in vivo. ChIP-Seq captures highly specific protein-DNA interactions, such as transcription factors (TFs) bound to appropriate binding sites, and sparse patterns formed by different histone marks. In this review, we focus on DNA sequence analysis methods adequate for TF ChIP-Seq data. We discuss numerous tasks starting from basic DNA motif finding and motif discovery as is, further applied to explore various features of experimental data. We show how sequence analysis of ChIP-Seq data derives novel biological knowledge on multiple levels, from individual transcription factor binding sites to genome segments operating as regulatory modules. Finally, we provide an overview of existing software in the field.
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