It has been well established that epigenetic mechanisms play an essential role in cell differentiation and maintenance of cell function. Not surprisingly, corruption of epigenetic machinery always results in disastrous consequences including oncogenesis.
Our research is focused on the epigenetic factor, histone variant H2A.B, that is mainly expressed in testis and involved in activation of gene expression and mRNA splicing in Round spermatids. Now we have a novel data showing that H2A.B is ectopically up-regulated in Hodgkin Lymphoma (HL) and evidently plays a role in HL pathogenesis. Hodgkin Lymphoma accounts for 5.6% of haematological cancers, yet very little is known about the mechanisms that drive HL carcinogenesis, especially the impact of epigenetic deregulation.
Our results show that H2A.B is highly expressed by malignant Hodgkin Reed-Sternberg (HRS) cells in all (n=81) HL patient samples tested. The ChIP-seq and RNA-seq analysis revealed that H2A.B is highly enriched on promoters, transcription start sites and a gene bodies of highly expressed genes, including oncogenes, that are known to contribute to HL pathogenesis, and many cancer-testis antigen (CTA) genes. Moreover, we have also detected enrichment of H2A.B in enlarged nucleoli of HRS cells and confirmed interaction between H2A.B and rDNA transcription machinery. Finally, our preliminary results have shown that HL–derived cells are “addicted” to H2A.B expression, as downregulation of H2A.B results in HL cell death. Thus, we hypothesise that the ability of H2A.B to de-compact chromatin and drive gene expression and splicing may be instrumental in HL cancer progression by driving expression of oncogenes and CTAs as well as by contributing to the overdrive of nucleolar activity. The implications of these findings will be discussed.