The Multifunctional Protein Nucleophosmin (NPM1) Is a Human Linker Histone H1 Chaperone

Linker histone H1 plays an essential role in chromatin organization. Proper deposition of linker histone as well as its removal is essential for chromatin dynamics and function. Linker histone chaperones perform this important task during chromatin assembly and other DNA-templated phenomena in the cell. Our in vitro data show that the multifunctional histone chaperone NPM1 interacts with linker histone HI through its first acidic stretch (residues 120-132). Association of NPM1 with linker histone Hi was also observed in cells in culture. NPM1 exhibited remarkable linker histone Hi chaperone activity, as it was able to efficiently deposit histone HI onto dinucleosomal templates. Overexpression of NPM1 reduced the histone H1 occupancy on the chromatinized template of HIV-1 LTR in TZM-bl cells, which led to enhanced Tat-mediated transactivation. These data identify NPM1 as an important member of the linker histone chaperone family in humans.