TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis

Jha, Kula N.; Tripurani, Swamy K.; Johnson, Gibbes R.

doi:10.1242/jcs.202721

Title: TSSK6 is required for γH2AX formation and the histone-to-protamine transition during spermiogenesis

Journal Article · Mon May 15 00:00:00 EDT 2017 · Journal of Cell Science

DOI:https://doi.org/10.1242/jcs.202721· OSTI ID:1350796

^[1]; Tripurani, Swamy K. ^[1]; Johnson, Gibbes R. ^[1]

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

ABSTRACT 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.

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Sponsoring Organization:: USDOE

OSTI ID:: 1350796

Alternate ID(s):: OSTI ID: 1783408

Journal Information:: Journal of Cell Science, Journal Name: Journal of Cell Science Vol. 130 Journal Issue: 10; ISSN 0021-9533

Publisher:: The Company of BiologistsCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 33 works

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