This ChIP protocol involves covalent cross-linking of protein-DNA complexes with formaldehyde followed by cell lysis and chromatin shearing. A ChIP-grade antibody (user supplied) is used with Protein A magnetic beads to immunoprecipitate the protein-DNA complexes of interest. Following reverse crosslinking, RNase A and Proteinase K treatments, the DNA is eluted in a minimal volume of buffer using a unique micro-elution spin column, eliminating the need for messy precipitations. The protocol has been optimized for efficient crosslinking, shearing, and immunoprecipitation regardless of the mammalian cell type. Additionally, eluted ChIP DNA is ideal for end point PCR, quantitative PCR, ChIPSeq library preparation, and Next-Gen sequencing-based applications.