Unraveling the Histone Replacement Pathway in Sperm

In somatic cells, DNA is wrapped around histone octamers in order to form a chromatin structure that is packed inside the nucleus. However, during human spermatogenesis approximately 85-90% of the histones in the DNA are replaced by an arginine rich protein called protamine. This allows for more efficient packaging of the DNA in the sperm cell. As a result, the sperm cell's movement is more hydrodynamic and the genetic material is protected. In this study we aim to understand the mechanics of DNA condensation in the nucleus of sperm cells. More specifically, we are interested in reconstructing the direct histone-protamine replacement pathway that occurs in fish. To study this phenomenon, we utilize a Tether Particle Motion (TPM) assay. In the TPM assay, a single DNA molecule is attached to a 1 μm "polystyrene bead on one end and is attached to a glass coverslip on the other. Using video microscopy, we track the motion of the bead and measure the length of the tether over time. When histones are replaced by protamine, we expect a change in the standard deviation of the DNA tether's movement due to further DNA compaction. Understanding this pathway has implications in biomaterial, epigenetic, and fertility research.