Phosphorylated H2B is found in condensed chromatin in dying cells.


DPNA gets condensed and chopped up during apoptosis. Despite these extensive changes, only one histone modification event—phosphorylation of histone H2B—has been specifically associated with apoptosis. Now, Wang Cheung, David Allis (University of Virginia, Charlottesville, VA), and colleagues provide evidence that this single change may be sufficient to induce the DNA changes during apoptosis.

Using a phosphospecific antibody, the authors identified the residue that is modified during apoptosis as a serine in the NH2-terminal tail of H2B. The antibody reacted with chromatin in dying cultured human cells and in clusters of cells undergoing apoptosis during tail resorption in developing frogs, indicating that the modification is well conserved.

The authors also show that the kinase responsible for H2B's death stamp is Mst1, which is cleaved at the onset of apoptosis by caspase-3. Mst1 phosphorylates H2B in vitro, and the cleaved form moves to the nucleus just before H2B phosphorylation in vivo. Expression of a truncated Mst1 induced H2B phosphorylation and DNA condensation and even led to cell death in the absence of proapoptotic insults. Although it is not clear how phosphorylation and condensation are linked, the authors found that phosphorylated H2B tends to aggregate in denaturing conditions and thus may be intrinsically sticky. Alternatively, phosphate-modified H2B may recruit some as-yet-unidentified protein that condenses DNA. ▪


Cheung, W., et al.