The chromatin immunoprecipitation (ChIP) assay, essential for studying such processes as transcriptional regulation, DNA replication, and DNA repair, relies on the cross-linking of proteins to DNA. Formaldehyde has been the most commonly used cross-linking reagent for ChIP assays. Although it has been highly effective for identifying proteins that bind directly to DNA, such as histones and transcription factors, it has not been as effective for examining proteins that might be associated with the DNA but are not located in as close proximity to the DNA, such as transcriptional coactivators and corepressors. Therefore, Zeng et al. tested a number of other cross-linking reagents. Of the four they tested, EGS, the largest molecule with the longest spacer arm, was the most effective. Cross-linking with formaldehyde and EGS facilitated successful immunoprecipitation of LKB1, a p53 binding protein, from the p21/Waf1 promoter. This combination of EGS/formaldehyde was also capable of immunoprecipitating the GATA-1 cofactors FOG-1 and MTA-1 from the locus control region upstream of the murine -globin locus, while formaldehyde alone was ineffective. -Page 694