The PureEpi™ chromatin preparation and optimization kit is designed for the preparation of samples for ChIP application. The kit’s materials, which include a set of validated reagents, may be used to enable chromatin preparation from either cultured cells or tissues. The kit also provides guidelines for generating sheared chromatin for ChIP. The protocol provided in the kit outlines a standard approach for chromatin preparation and includes tips for avoiding common pitfalls. Additional sections demonstrate how modifications to key parameters such as fixation and sonication conditions impact chromatin quality and ChIP performance.