H3.3 replacement facilitates epigenetic reprogramming of donor nuclei in somatic cell nuclear transfer embryos

Duancheng Wen, Laura A. Banaszynski, Zev Rosenwaks, C. David Allis, Shahin Rafii

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Transfer of a somatic nucleus into an enucleated oocyte is the most efficient approach for somatic cell reprogramming. While this process is known to involve extensive chromatin remodeling of the donor nucleus, the maternal factors responsible and the underlying chromatin-based mechanisms remain largely unknown. Here we discuss our recent findings demonstrating that the histone variant H3.3 plays an essential role in reprogramming and is required for reactivation of key pluripotency genes in somatic cell nuclear transfer (SCNT) embryos. Maternal-derived H3.3 replaces H3 in the donor nucleus shortly after oocyte activation, with the amount of replacement directly related to the differentiation status of the donor nucleus in SCNT embryos. We provide additional evidence to suggest that de novo synthesized H3.3 replaces histone H3 carrying repressive modifications in the donor nuclei of SCNT embryos, and hypothesize that replacement may occur at specific loci that must be reprogrammed for gene reactivation.

Original languageEnglish (US)
Pages (from-to)369-375
Number of pages7
JournalNucleus
Volume5
Issue number5
DOIs
StatePublished - Aug 25 2014

Keywords

  • Chromatin remodeling
  • H3K27me3
  • Histone H3.3
  • Nuclear reprogramming
  • SCNT

ASJC Scopus subject areas

  • Cell Biology

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