Heritable sperm chromatin epigenetics: a break to remember.

Sperm chromatin not only has a unique structure to condense and protect the paternal DNA in transit, but also provides epigenetic information that supports embryonic development. Most of the unique sperm nuclear architecture is formed during the sweeping postmeiotic chromatin remodeling events in spermiogenesis, where the majority of nucleosomes are removed and replaced by protamines. The remaining histones and other chromatin proteins are located in structurally and transcriptionally relevant positions in the genome and carry diverse post-translational modifications relevant to the control of embryonic gene expression. How such postmeiotic chromatin-based programming of sperm epigenetic information proceeds, and how susceptible the process is to modulation by exogenous factors are key questions for understanding the inheritance of acquired epigenetic marks through the male germ line. We propose that transient DNA strand breaks mediated by topoisomerase II beta and the subsequent activation of DNA damage response pathways result in defined post-translational modifications of histones in spermiogenesis. These pathways, likely along with others, may contribute to chromatin remodeling in elongating spermatids, influence chromatin-based intergenerational inheritance of epigenetic information, and may be defective in pathologies of abnormal male gametogenesis and infertility.