Diagram of iPOND methodology. Cells are labeled with EdU for a short time, and proteins are crosslinked to DNA. Cells are permeabilized, and a click reaction performed to conjugate biotin to the EdU. Sonication and cell lysis is followed by purification using a streptavidin matrix. Proteins are eluted and crosslinks reversed prior to detection by either immunoblotting or mass spectrometry. See Sirbu et al, Genes and Development 2011 for more details.