Spermatogenesis in mammals results in sperm that have a nucleus that is 40 times smaller than an average somatic cell. Thus, the sperm haploid genome must be packaged very tightly, yet in a way that is reversible after fertilization. This sperm-specific DNA compaction is due to a nucleosome-to-nucleoprotamine transition, where the histone-based nucleosomes are removed and replaced with arginine-rich protamine proteins that facilitate a tighter packaging of DNA. In 2013 Montellier et al. showed that replacement of the H2B protein in the nucleosomes with a testis-specific variant of H2B called TSH2B is a critical step prior to the nucleosome-to-nucleoprotamine transition. Mice lacking TSH2B retain H2B and their sperm arrest late in spermatogenesis with reduced DNA compaction. Based on these findings, would you expect that TSH2B-containing nucleosomes are more or less stable than H2B-containing nucleosomes? Explain your reasoning.

Key Concepts

Spermatogenesis

Spermatogenesis is the process by which male gametes, or sperm cells, are produced in the testes. It involves several stages, including mitosis, meiosis, and spermiogenesis, leading to the formation of mature sperm. This process is crucial for sexual reproduction and is characterized by significant cellular changes, including DNA compaction to fit within the sperm nucleus.

Nucleosome-to-Nucleoprotamine Transition

The nucleosome-to-nucleoprotamine transition is a critical step in sperm development where histone proteins, which package DNA into nucleosomes, are replaced by protamines. This transition allows for a much tighter packing of DNA, essential for the small size of the sperm nucleus. Protamines are arginine-rich proteins that facilitate this compaction, making the DNA more stable and less accessible until fertilization.

Histone Variants and Stability

Histone variants, such as TSH2B, can influence the stability and functionality of nucleosomes. The incorporation of testis-specific histone variants may alter the interactions between DNA and histones, potentially affecting the overall stability of the nucleosome structure. In the context of spermatogenesis, the presence of TSH2B instead of H2B is suggested to play a role in preparing the chromatin for the subsequent transition to protamines, impacting DNA compaction and stability.