Caspase-mediated changes in histone H1 in early apoptosis: prolonged caspase activation in developing olfactory...

Programmed cell death or apoptosis is required for the patterning and development of multicellular organisms. However, apoptosis is a difficult process to measure because the dead cells are rapidly degraded by their neighbors within a few hours. The post-caspase activation events that determine whether a cell will undergo apoptosis remain elusive. Here we report that apoptosis-specific nuclear events that occur before DNA fragmentation can be distinguished by monitoring the histone H1 status. In both mammals and Drosophila, dying cells failed to be immunolabeled with an anti-H1 monoclonal antibody, AE-4. Real-time imaging of caspase activation and H1 dynamics in mammalian neural cells revealed that H1 changed its location in the nucleus after caspase activation. In addition, the timing of this re-localization was largely dependent on the apoptotic stimulus used. From the staining patterns of AE-4 and anti-active caspase-3 antibodies, cells undergoing the transition from caspase activation to the apoptotic H1 change could be identified as H1-positive caspase-activated cells, providing a novel criterion for early apoptosis and making it possible to characterize caspase-activated cells in tissues. On the basis of these staining patterns, we found that many olfactory sensory neurons in the developing mouse olfactory epithelium showed sustained caspase activity without the H1 change, suggesting a unique caspase function in these neurons.