ChIP-seq (57, 58) is the sequencing of DNA that has been reversibly bound to protein and pulled down by immunoprecipitation, an evolution of ChIP-chip analysis which used hybridization on tiled arrays instead of sequencing (see Figure 3). Although the name implies that the proteins of interest are in the context of chromatin, any DNA associating protein can be analyzed. The method allows the identification of the DNA sequences at the location of interaction, and it has been used extensively in the study of epigenetic modifications where the modified histones are used for immunoprecipitation, but also in the study of nucleosome positioning and transcription factor binding. The additional information provided by ChIP-seq compared to ChIP-chip will enhance and accelerate our functional annotation of the genome sequence and bring us one step closer to linking DNA variation to function and to disease.
