How mammals pack their sperm: a variant matter

Abstract

Producing competent gametes is essential for transmitting genetic information throughout generations. Spermatogenesis is a unique example of rearrangements of genome packaging to ensure fertilization. After meiosis, spermatids undergo drastic morphological changes, perhaps the most dramatic ones occurring in their nuclei, including the transition into a protamine-packaged genome. In this issue of Genes & Development, Montellier and colleagues (pp. 1680-1692) shed new light on the molecular mechanisms regulating this transition by ascribing for the first time a function to a histone variant, TH2B, in the regulation of this process.

Keywords: BRDT; H2AZ; histone eviction; male contraception; male infertility; reprogramming; sex chromosome inactivation.

Figure 1.

Changes in histone variant composition allow a smooth transition from a nucleosome-based toward a protamine-packed DNA during spermatogenesis. In elongating spermatids, histone variants are enriched in the sperm chromatin. Among them, TH2B becomes incorporated into chromatin on a global scale, and this precedes histone replacement in condensing spermatids. The addition of a His/Flag/HA tag in the C terminus of TH2B disturbs its replacement and results instead in defective protamine incorporation, which leads to male sterility. In the TH2B-null mouse model, the process of protamine incorporation occurs normally, and TH2B absence is suggested to be balanced through the acquisition of compensatory histone modifications on the core histones H2B, H3, and H4.