Marking dad's centromeres: maintaining CENP-A in sperm

Chromosome Res. 2025 Apr 26;33(1):8. doi: 10.1007/s10577-025-09766-2.

Abstract

During spermiogenesis, histones are removed from most genomic loci and are replaced by protamines in mature sperm nuclei. Yet, centromeres appear resistant to this process. We review the experimental evidence that the centromeric histone CENP-A is maintained in mature sperm nuclei, comparing human, bovine, mouse and fly species. We also recall how the detection of centromeres in mature sperm nuclei in the 1990's contributed to the isolation of the CENP-A protein and the eventual cloning of the human CENP-A gene. Further, based on more recent genetic studies carried out in flies and in mice, we discuss the inheritance and functional importance of paternal CENP-A and how it is complemented by maternal CENP-A to give rise to a healthy embryo. Finally, we raise some unanswered questions regarding the exclusive maintenance of CENP-A on sperm, the organisation of sperm centromeric chromatin and its importance for fertility and early embryo development.

Keywords: CENP-A; Centromere; Gamete; Histone; Male fertility; Sperm.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantigens* / genetics
  • Autoantigens* / metabolism
  • Cattle
  • Centromere Protein A
  • Centromere* / genetics
  • Centromere* / metabolism
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone* / genetics
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Humans
  • Male
  • Mice
  • Spermatogenesis / genetics
  • Spermatozoa* / metabolism

Substances

  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Autoantigens
  • CENPA protein, human
  • Chromatin
  • Cenpa protein, mouse