Hira-Mediated H3.3 Incorporation Is Required for DNA Replication and Ribosomal RNA Transcription in the Mouse Zygote

Chih-Jen Lin, Fong Ming Koh, Priscilla Wong, Marco Conti, Miguel Ramalho-Santos

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)268-279
Number of pages12
JournalDevelopmental Cell
Volume30
Issue number3
Early online date31 Jul 2014
DOIs
Publication statusPublished - 11 Aug 2014

Keywords

  • HISTONE VARIANT H3.3
  • PREIMPLANTATION DEVELOPMENT
  • POLYMERASE I
  • MATERNAL CHROMATIN
  • MEIOTIC MATURATION
  • GENE-EXPRESSION
  • GENOME-WIDE
  • OOCYTES
  • EMBRYOS
  • DEGRADATION

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