Poly(ADP-ribose) metabolism is essential for proper nucleoprotein exchange during mouse spermiogenesis

Mirella L. Meyer-Ficca, Motomasa Ihara, Julia D. Lonchar, Marvin L. Meistrich, Caroline A. Austin, Wookee Min, Zhao Qi Wang, Ralph G. Meyer

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Sperm chromatin is organized in a protamine-based, highly condensed form, which protects the paternal chromosome complement in transit, facilitates fertilization, and supports correct gene expression in the early embryo. Very few histones remain selectively associated with genes and defined regulatory sequences essential to embryonic development, while most of the genome becomes bound to protamine during spermiogenesis. Chromatin remodeling processes resulting in the dramatically different nuclear structure of sperm are poorly understood. This study shows that perturbation of poly(ADP-ribose) (PAR) metabolism, which is mediated by PAR polymerases and PAR glycohydrolase in response to naturally occurring endogenous DNA strand breaks during spermatogenesis, results in the abnormal retention of core histones and histone linker HIST1H1T (H1t) and H1-like linker protein HILS1 in mature sperm. Moreover, genetic or pharmacological alteration of PAR metabolism caused poor sperm chromatin quality and an abnormal nuclear structure in mice, thus reducing male fertility.

Original languageEnglish
Pages (from-to)218-228
Number of pages11
JournalBiology of Reproduction
Volume84
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

Keywords

  • Chromatin remodeling
  • Condensation
  • Histone h1 linker
  • PARG
  • PARP
  • Poly(ADP)ribose
  • Poly(ADP-ribose) glycohydrolase
  • Poly(ADP-ribose) polymerase
  • Sperm
  • Spermatid
  • Spermatogenesis
  • Spermiogenesis
  • TOP2A
  • TOP2B
  • Testis
  • Topoisomerase II beta
  • Transition protein

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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