GSE208779
A novel H2B variant with TERRA-promoter enrichment, H2BW2, forms decompacted nucleosomes in human spermatogenesis
During spermatogenesis, histones are gradually replaced by testis-specific histone variants, transition proteins, and eventually protamine in elongating spermatids. H2BW2 is a mammalian testis-specific histone H2B variant. The amino acid sequence of H2BW2 is relatively close to another primate testis-specific histone variant H2BFWT, however, there is very little known about the functions of H2BW2. Here, we found that H2BW2 destabilizes nucleosomes by reducing the interactions between histone H2A-H2BW2 dimers and DNA. These interactions may be reduced by changing to less positive surface charge in the alpha 1 helix of H2BW2, and amino acids to neutral or negative charge residues in loop 1 and the acidic patch. Single-molecule optical tweezers assay shows that the H2BW2 nucleosome destabilizes the interactions between H2A-H2B and DNA by affecting both unwrapping and rewrapping rates, and decreases the energy barrier of their interactions by ~35%. Importantly, H2BW2 was highly enriched in the telomere repeat-containing RNA (TERRA) promoters in human testis. The presence of H2BW2 in the TERRA promoter upregulated TERRA expressions and associated with longer telomeres. Our results suggest that H2BW2 participates in the maintenance of telomere length by enhancing the expression of TERRA in early spermatogenesis. Overall design: Explore the distribution of H2BW2 in the genome within the human testis from two donors and stable expression HeLa cells.