• PMID: 28389581
• Gene Name: TSSK6
• Condition: Spermiogenesis, male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Spermiogenesis, male infertility

TSSK6 is required for ?H2AX formation and the histone-to-protamine transition during spermiogenesis

Jha KN, Tripurani SK, Johnson GR.

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 (γH2AX), 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 γH2AX 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 γH2AX 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 γH2AX formation during spermiogenesis, and also link γH2AX to the histone-to-protamine transition and male fertility. CI - © 2017. Published by The Company of Biologists Ltd. FAU - Jha, Kula N AU - Jha KN AUID- ORCID: 0000-0002-2218-1864 AD - Division of Biotechnology Review and Research IV, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA kula.jha@fda.hhs.gov gibbes.johnson@fda.hhs.gov. FAU - Tripurani, Swamy K AU - Tripurani SK AD - Division of Biotechnology Review and Research IV, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.