Alteration of poly(ADP-ribose) metabolism affects murine sperm nuclear architecture by impairing pericentric heterochromatin condensation

Mirella L. Meyer-Ficca, Julia D. Lonchar, Motomasa Ihara, Jessica J. Bader, Ralph G. Meyer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The mammalian sperm nucleus is characterized by unique properties that are important for fertilization. Sperm DNA retains only small numbers of histones in distinct positions, and the majority of the genome is protamine associated, which allows for extreme condensation and protection of the genetic material. Furthermore, sperm nuclei display a highly ordered architecture that is characterized by a centrally located chromocenter comprising the pericentromeric chromosome regions and peripherally positioned telomeres. Establishment of this unique and well-conserved nuclear organization during spermiogenesis is not well understood. Utilizing fluorescence in situ hybridization (FISH), we show that a large fraction of the histone-associated sperm genome is repetitive in nature, while a smaller fraction is associated with unique DNA sequences. Coordinated activity of poly(ADP-ribose) (PAR) polymerase and topoisomerase II beta has been shown to facilitate DNA relaxation and histone to protamine transition during spermatid condensation, and altered PAR metabolism is associated with an increase in sperm histone content. Combining FISH with three-dimensional laser scanning microscopy technology, we further show that altered PAR metabolism by genetic or pharmacological intervention leads to a disturbance of the overall sperm nuclear architecture with a lower degree of organization and condensation of the chromocenters formed by chromosomal pericentromeric heterochromatin.

Original languageEnglish
Pages (from-to)319-335
Number of pages17
JournalChromosoma
Volume122
Issue number4
DOIs
Publication statusPublished - 2013 Aug 1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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