DNA replication requires the chromatin to be in an accessible open state, which is facilitated by histone acetylation. The five members of the INhibitors of Growth family of tumor suppressors recruit histone acetylation and deacetylation complexes to the chromatin. They are frequently downregulated and, less frequently, mutated in tumors.

ING proteins contain a conserved N-terminal domain (Nt), a central disordered region with the nuclear localization sequence (NLS), and a C-terminal PlantHomeoDomain (PHD). The PHD binds histone H3 trimethylated at K4, a mark of chromatin sites active in transcription.

ING4 and ING5 dimerize through their Nt domain, and the same may happen with the other ING proteins. As bivalent readers of the H3K4me3 mark, they may engage two histones from the same or different nucleosomes. Dimerization deficient mutants found in tumors decrease their anticancer properties. The central disordered regions bind DNA and contribute to the overall affinity of ING proteins for the chromatin, which also increases in the crowded nucleoplasm, as indicated by NMR measurements in solutions with crowding agents.

A homodimer of ING4 or ING5 binding the two histone H3 N-termainal tails of a single nucleosome through their PHD
Model of a dimer of ING4 (or ING5) binding the two histone H3 of a nucleosome through the PHD fingers