Figure 6. Graphic representation of the ChIP-on-chip method. ChIP-on-chip combines Chromatin Immunoprecipitation with microarray technologies. In the initial step of this method proteins are cross-linked on the DNA usually with gentle formaldehyde fixation that is reversible. Then, the cells are lysed and the DNA is sheared by sonication or nuclease treatment. This results in double-stranded DNA fragments normally less than 1 kb in length. The DNA/protein complexes can be immunoprecipitated with appropriate antibodies against histone modifications (or against methylated cytosines in the Methylated DNA ChIP assay-MeDIP). After reversing the cross-linking and a step of amplification, the immunoprecipitation as well as the input DNA can be differentially labeled and hybridized to genomic microarrays (ChIP-on chip).