| First Author | Jha KN | Year | 2017 |
| Journal | J Cell Sci | Volume | 130 |
| Issue | 10 | Pages | 1835-1844 |
| PubMed ID | 28389581 | Mgi Jnum | J:253146 |
| Mgi Id | MGI:5924821 | Doi | 10.1242/jcs.202721 |
| Citation | Jha KN, et al. (2017) TSSK6 is required for gammaH2AX formation and the histone-to-protamine transition during spermiogenesis. J Cell Sci 130(10):1835-1844 |
| abstractText | Spermiogenesis includes transcriptional silencing, chromatin condensation and extensive morphological changes as spermatids transform into sperm. Chromatin condensation involves histone hyperacetylation, transitory DNA breaks, histone H2AX (also known as H2AFX) phosphorylation at Ser139 (gammaH2AX), and replacement of histones by protamines. Previously, we have reported that the spermatid protein kinase TSSK6 is essential for fertility in mice, but its specific role in spermiogenesis is unknown. Here, we show that TSSK6 expression is spatiotemporally coincident with gammaH2AX formation in the nuclei of developing mouse spermatids. RNA-sequencing analysis demonstrates that genetic ablation of Tssk6 does not impact gene expression or silencing in spermatids. However, loss of TSSK6 blocks gammaH2AX formation, even though the timing and level of the transient DNA breaks is unaltered. Further, Tssk6-knockout sperm contained increased levels of histones H3 and H4, and protamine 2 precursor and intermediate(s) indicative of a defective histone-to-protamine transition. These results demonstrate that TSSK6 is required for gammaH2AX formation during spermiogenesis, and also link gammaH2AX to the histone-to-protamine transition and male fertility. |
