Optimized protocols for chromatin immunoprecipitation of exogenously expressed epitope-tagged proteins

Chromatin immunoprecipitation (ChIP) assay is widely used for investigating the interaction between DNA and DNA-binding proteins such as transcription factors, co-factors, or chromatin-associated proteins. However, a successful ChIP assay largely depends on the quality of a ChIP-grade primary antibody. In cases where specific antibodies are unavailable or with low binding affinity, here, we describe a tailored protocol to achieve robust and reproducible chromatin binding by expressing an exogenous epitope-tagged protein in cells, followed by ChIP assays using a tag-specific antibody. For complete details on the use and execution of this protocol, please refer to Fang et al. (2021)¹ and Kidder et al. (2011).²