EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice

Mol Cell Biol. 2017 Sep 12;37(19):e00082-17. doi: 10.1128/MCB.00082-17. Print 2017 Oct 1.

Abstract

Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome.

Keywords: EPC1; TIP60; histone acetylation; mouse; spermatids; spermiogenesis.

MeSH terms

  • Acetylation
  • Animals
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Histones / metabolism*
  • Lysine Acetyltransferase 5
  • Male
  • Mice
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Spermatids / growth & development*
  • Spermatids / metabolism
  • Spermatogenesis*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Epc1 protein, mouse
  • Histones
  • Repressor Proteins
  • Trans-Activators
  • Histone Acetyltransferases
  • Kat5 protein, mouse
  • Lysine Acetyltransferase 5