Pinpointing the Genomic Localizations of Chromatin-Associated Proteins: The Yesterday, Today, and Tomorrow of ChIP-seq

Chromatin-associated proteins are instrumental for controlling spatiotemporal gene expression. Determining where these proteins bind across the genome is critical for understanding gene regulation. A widely used technique at present is ChIP-seq, which leverages chromatin fragmentation, antibody-mediated enrichment, next-generation sequencing, and data analysis to uncover the genomic sequences and patterns of protein-DNA interactions. In this article, we will provide an overview of how ChIP-seq was developed, the key elements of the experimentation and data analysis pipeline, and the recent variations that push the boundaries of precision and cell number requirements. We will also briefly discuss how future development of ChIP-seq may further advance our understanding of chromatin biology. © 2019 by John Wiley & Sons, Inc.