Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Cell Rep. 2017 Jan 17;18(3):593-600. doi: 10.1016/j.celrep.2016.12.065.

Abstract

Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.

Keywords: chromatin; crystal structure; epigenetics; histone variant; meiosis; nucleosome; spermatogenesis; spermatogonial differentiation; spermatozoa; testes.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Sequence
  • Animals
  • Azoospermia / etiology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Haploidy
  • Histones / chemistry
  • Histones / deficiency
  • Histones / genetics*
  • Male
  • Meiosis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism
  • Spermatogenesis
  • Spermatogonia / metabolism*
  • Testis / metabolism*
  • Testis / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Chromatin
  • Histones
  • Nucleosomes
  • REC8 protein, human
  • Stra8 protein, mouse