Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote

Dev Cell. 2014 Aug 11;30(3):268-79. doi: 10.1016/j.devcel.2014.06.022. Epub 2014 Jul 31.


Extensive chromatin reprogramming occurs at fertilization and is thought to be under the control of maternal factors, but the underlying mechanisms remain poorly understood. We report that maternal Hira, a chaperone for the histone variant H3.3, is required for mouse development past the zygote stage. Male pronucleus formation is inhibited upon deletion of Hira due to a lack of nucleosome assembly in the sperm genome. Hira mutant oocytes are incapable of developing parthenogenetically, indicative of a role for Hira in the female genome. Both parental genomes show highly reduced levels of DNA replication and transcription in the mutants. It has long been thought that transcription is not required for zygote development. Surprisingly, we found that Hira/H3.3-dependent transcription of ribosomal RNA is required for first cleavage. Our results demonstrate that Hira-mediated H3.3 incorporation is essential for parental genome reprogramming and reveal an unexpected role for rRNA transcription in the mouse zygote.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly / physiology*
  • DNA Replication / genetics*
  • DNA Replication / physiology
  • Fertilization / genetics
  • Fertilization / physiology
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • RNA, Ribosomal / metabolism*
  • Spermatozoa / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Zygote / growth & development
  • Zygote / metabolism*


  • Cell Cycle Proteins
  • Chromatin
  • Hira protein, mouse
  • Histone Chaperones
  • Histones
  • RNA, Ribosomal
  • Transcription Factors