Epigenetic-based mechanisms are essential for cell differentiation and function but how exactly epigenetic control is transmitted and interpreted is poorly understood. One of the most crucial and dramatic examples of epigenetic regulation is during spermatogenesis. Male germ cells undergo sequential differentiation steps within seminiferous tubules all tightly epigenetically controlled, to ensure that chromatin is remodeled in a tight spatio-temporal manner, in order to produce one of the most specialised cell types: mature spermatozoa.
Our work is focused on deciphering a role of a spermatid-specific histone variant, H2A.B3, in spermatid differentiation. We have previously shown that histone variant H2A.B3 is expressed in haploid round spermatids and participates in activation of the male germ cell expression program1. Uniquely, this histone variant can bind directly to both DNA and RNA and participate in RNA processing2. To investigate the function of H2A.B3 is spermiogenesis further, we have generated a knock-out (KO) H2A.B3 mouse. The have found that H2A.B3 KO male mice are sub-fertile, that is likely due to deregulation of RNA Pol II transcription and down-regulation of expression of key spermiogenesis-specific genes3. The H2A.B3 KO also results in the production of defective sperm. Unexpectedly, we have found that absence of H2A.B3 in haploid germ cells affects histone-protamine exchange and even more surprisingly, the function of somatic Sertoli cells.