Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos

This study investigates the role of H3K9me3, an epigenetic mark, in the inefficient reprogramming of somatic cells via somatic cell nuclear transfer (SCNT). The researchers found that residual H3K9me3 in SCNT embryos interferes with the activation of the embryonic genome and proper cell fate determination. The researchers discovered that H3K9me3 modifications in somatic cells can act as a barrier to cell fate changes. They also observed that these modifications prevent regions from being activated in 2-cell SCNT embryos. The study identified MAX and MCRS1 as potential regulators of H3K9me3 deposition and found that overexpression of these factors significantly improves SCNT embryo development and lineage specification.

• 1
  SCNT embryos exhibit genome-wide excess H3K9me3 modification throughout preimplantation development, differing significantly from fertilized embryos.
• 2
  Unreprogrammed H3K9me3 blocks the activation of minor zygotic genome activation (ZGA) genes and delays the activation of repeat elements in SCNT embryos.
• 3
  Lineage-specific H3K9me3 deposition is indistinct in SCNT embryos during the first cell fate determination, suggesting a defect in lineage commitment.