Every cell within an organism contains the same genome, yet each specific cell type only allows expression of a subset of genes that defines its function. To achieve this, very precise DNA handling mechanisms must be in place. One such mechanism is epigenetic regulation of genome. Epigenetic regulation functions on multiple levels: from gene expression to DNA repair to flawless division of chromatin between daughter cells during mitosis. However, one of the most dramatic examples of epigenetic regulation is during spermiogenesis. Indeed, spermatozoa are the only cell type that is destined to leave the parental organism and ultimately, outlive it. To achieve this, haploid spermatids undergo sequential differentiation steps, all tightly controlled by epigenetic machinery, so that, acrosome and flagellum are formed, nucleus is markedly condensed and cytoplasm is lost. To begin this transformation, a robust gene activation program must be switched on by round spermatids at the onset of spermatogenesis.
Here, I will discuss a new role for H2A histone variants in regulation of gene activation and mRNA splicing in round spermatids. Our findings show that testis-specific histone variant, mH2A.B/H2A.Lap1, is associated with transcription start sites of actively transcribed genes, co-localises and interacts with RNA Pol II complex subunits and, unexpectedly, interacts with a number of RNA-binding proteins that control pre-mRNA splicing. Interestingly, our immunofluorescence staining and subcellular fractionation of round spermatids revealed that a major fraction of mH2A.B, while still being bound to chromatin, localized within splicing speckles with actively transcribing RNA Pol II complex and RNA processing factors, showing that mH2A.B associates not only with DNA but also with RNA, specifically at the sites of splicing. Finally, we showed that N-terminus of mH2A.B directly binds RNA. This is a first report, to our knowledge, of direct interaction between a histone N-terminal tail and RNA.