Mammalian-specific H2A variant, H2ABbd, is Involved in Apoptotic Induction via Activation of NF-{kappa}B Signaling Pathway [DNA and Chromosomes]

February 28th, 2014 by Goshima, T., Shimada, M., Sharif, J., Matsuo, H., Misaki, T., Johmura, Y., Murata, K., Koseki, H., Nakanishi, M.

Histone variants play specific roles in maintenance and regulation of chromatin structures. H2ABbd, an H2A variant, possesses a highly divergent structure compared to canonical H2A and is highly expressed in post-meiotic 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 post-meiotic germ cell development, suggesting that H2ABbd might influence transcription. Taken together, our data suggests that H2ABbd may contribute to specific chromatin structures and promote NF-κB activation, which could in turn induce apoptosis in mammalian cells.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Mammalian-specific H2A variant, H2ABbd, is Involved in Apoptotic Induction via Activation of NF-{kappa}B Signaling Pathway [DNA and Chromosomes]