Q&A: ChIP-seq technologies and the study of gene regulation

ChIP-seq is short for chromatin immunoprecipitationsequencing. Fundamentally, ChIP-seq is the sequencing of the genomic DNA fragments that co-precipitate with a DNA-binding protein that is under study. The DNAbinding proteins most frequently investigated in this way are transcription factors (for example, p53 or NFκB), chromatin-modifying enzymes (for example, p300, histone deacetylases), modified histones interacting with genomic DNA (for example, histone 3 trimethylated on lysine 4), and components of the basal transcriptional machinery (for example, RNA polymerase II). Theoretically, this technology can identify, in an unbiased manner, all DNA segments in the genome physically associated with a specific DNA-binding protein. We say ‘unbiased’ because whatever DNA comes down in the immunoprecipitate will be sequenced, and thus the technique does not rely on prior knowledge of precise DNA binding sites.