Mitotic fidelity requires transgenerational action of a testis-restricted HP1.

Mia T Levine,Harmit S Malik,Helen M Vander Wende

doi:10.7554/elife.07378

Abstract

Sperm-packaged DNA must undergo extensive reorganization to ensure its timely participation in embryonic mitosis. Whereas maternal control over this remodeling is well described, paternal contributions are virtually unknown. In this study, we show that Drosophila melanogaster males lacking Heterochromatin Protein 1E (HP1E) sire inviable embryos that undergo catastrophic mitosis. In these embryos, the paternal genome fails to condense and resolve into sister chromatids in synchrony with the maternal genome. This delay leads to a failure of paternal chromosomes, particularly the heterochromatin-rich sex chromosomes, to separate on the first mitotic spindle. Remarkably, HP1E is not inherited on mature sperm chromatin. Instead, HP1E primes paternal chromosomes during spermatogenesis to ensure faithful segregation post-fertilization. This transgenerational effect suggests that maternal control is necessary but not sufficient for transforming sperm DNA into a mitotically competent pronucleus. Instead, paternal action during spermiogenesis exerts post-fertilization control to ensure faithful chromosome segregation in the embryo.

Highlights

Faithful chromosome segregation requires careful orchestration of chromosomal condensation, alignment, and movement of mitotic chromosomes during every eukaryotic cell division (Rhind and Russell, 2012)
No such cell cycle checkpoint proteins have been identified to act in the very first embryonic mitotic cycle (O’Farrell et al, 2004), which must accomplish the difficult task of synchronizing maternal and paternal chromosomes that were inherited in very different chromatin states
To investigate the paternal contributions that ensure timely participation of the paternal genome in early embryogenesis, we carried out a detailed functional analysis of the testisrestricted Heterochromatin Protein 1E (HP1E) gene in D. melanogaster

Summary

Introduction

Faithful chromosome segregation requires careful orchestration of chromosomal condensation, alignment, and movement of mitotic chromosomes during every eukaryotic cell division (Rhind and Russell, 2012). The very first embryonic mitosis in animals requires additional synchronization. And maternally inherited genomes undergo independent chromatin reorganization and replication prior to mitotic entry. The sperm-deposited, paternal chromosomes must undergo an even more radical transition from a highly compact, protamine-rich state to a decondensed, histone-rich state before DNA replication (Braun, 2001; Miller et al, 2010). Despite these divergent requirements to achieve replication- and mitotic-competency, maternal and paternal genomes synchronously enter the first mitosis. Failure to carry out paternal chromosome remodeling in a timely fashion results in paternal genome loss and embryonic inviability (Loppin et al, 2001; McLay and Clarke, 2003; Landmann et al, 2009)

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Conclusion