In vivo formaldehyde cross-linking: it is time for black box analysis

Formaldehyde cross-linking is an important component of many technologies, including chromatin immunoprecipitation and chromosome conformation capture. The procedure remains empirical and poorly characterized, however, despite a long history of its use in research. Little is known about the specificity of in vivo cross-linking, its efficiency and chemical adducts induced by the procedure. It is time to search this black box.