The chromodomain (CD) is a highly conserved motif present in a variety of animal 
and plant proteins, and its probable role is to assemble a variety of 
macromolecular complexes in chromatin. The importance of the CD to the survival 
of mammalian cells has been tested. Accordingly, we have ablated CD function 
using two single-chain intracellular Fv (scFv) fragments directed against 
non-overlapping epitopes within the HP1 CD motif. The scFv fragments can 
recognize both CD motifs of HP1 and Polycomb (Pc) in vitro and, when expressed 
intracellularly, interact with and dislodge the HP1 protein(s) from their 
heterochromatin localization in vivo. Mouse and human fibroblasts expressing 
anti-chromodomain scFv fragments show a cell-lethal phenotype and an apoptotic 
morphology becomes apparent soon after transfection. The mechanism of cell death 
appears to be p53 independent, and the cells are only partly rescued by 
incubation with the wide spectrum caspase inhibitor Z-VAD fmk. We conclude that 
expression of anti-chromodomain intracellular antibodies is sufficient to 
trigger a p53-independent apoptotic pathway that is only partly dependent on the 
known Z-VAD-inhibitable caspases, suggesting that CD function is essential for 
cell survival.