Mammal-specific H2A Variant, H2ABbd, Is Involved in Apoptotic Induction via Activation of NF-κB Signaling Pathway

Histone variants play specific roles in maintenance and regulation of chromatin structures. H2ABbd, an H2A variant, possesses a highly divergent structure compared with canonical H2A and is highly expressed in postmeiotic germ cells, but its functions in the regulation of gene expression are largely unknown. In the present study, we investigated the cellular phenotype associated with enforced H2ABbd expression. Among H2A variants, H2ABbd specifically caused growth defect in human cells and induced apoptosis. H2ABbd expression resulted in degradation of inhibitor of κB-α and translocation of NF-κB into nuclei, indicating the activation of NF-κB. Intriguingly, NF-κB activity was essential for H2ABbd-induced apoptosis. H2ABbd overexpression resulted in DNA damage after release from G1/S, progressed through the S phase slowly, and induced apoptosis. Furthermore, gene expression microarray analysis revealed that expression of H2ABbd activates groups of genes involved in apoptosis and postmeiotic germ cell development, suggesting that H2ABbd might influence transcription. Taken together, our data suggest that H2ABbd may contribute to specific chromatin structures and promote NF-κB activation, which could in turn induce apoptosis in mammalian cells. H2ABbd is an H2A variant possessing a highly divergent structure. However, the in vivo function of H2ABbd is not understood. Expression of H2ABbd caused DNA damage, induced apoptotis, and finally led to cell death. H2ABbd caused apoptosis in caspase 3- and NF-κB-dependent manners. This work describes a novel role for human H2ABbd in gene regulation and cell death.