DNA in eukaryotic cells is packaged into chromatin by histones. Chromatin is a highly dynamic and hierarchical structure. It plays an essential role in regulation of gene expression and silencing. The primary structure of chromatin comprises of an array of repeating units, the nucleosomes. Within a nucleosome, DNA is wrapped around eight histones, two H2A-H2B dimers and a H3-H4 tetramer, and neighbouring nucleosomes are linked by a histone H1. Importantly, replacement of one histone subunit with a histone variant enables the formation of different specialized chromatin structures. Therefore, in order to understand how chromatin regulates genome function, we study histone variants, which are in fact natural histone mutants, to investigate alterations in the structure and function of chromatin in the presence of such variants.
Recently, we have identified a unique mouse H2A histone variant, H2A.Lap1 (Lack of Acidic Patch), as a novel component of the Transcription Start Site (TSS) of active genes expressed during specific stages of spermatogenesis. This unique chromatin landscape at the TSS also includes a second histone variant, H2A.Z. In the latter stages of round spermatid development, H2A.Lap1 dynamically loads onto the inactive X chromosome, enabling the transcriptional activation of previously repressed genes. We therefore propose that H2A.Lap1 is involved in a new chromatin-based mechanism of transcriptional activation, which will have important implications in understanding how cellular differentiation is achieved.