Abstract
The pericentromeric heterochromatin of one-cell embryos forms a unique, ring-like structure around the nucleolar precursor body, which is absent in somatic cells. Here, we found that the histone H3 variants H3.1 and/or H3.2 (H3.1/H3.2) were localized asymmetrically between the male and female perinucleolar regions of the one-cell embryos; moreover, asymmetrical histone localization influenced DNA replication timing. The nuclear deposition of H3.1/3.2 in one-cell embryos was low relative to other preimplantation stages because of reduced H3.1/3.2 mRNA expression and incorporation efficiency. The forced incorporation of H3.1/3.2 into the pronuclei of one-cell embryos triggered a delay in DNA replication, leading to developmental failure. Methylation of lysine residue 27 (H3K27me3) of the deposited H3.1/3.2 in the paternal perinucleolar region caused this delay in DNA replication. These results suggest that reduced H3.1/3.2 in the paternal perinucleolar region is essential for controlled DNA replication and preimplantation development. The nuclear deposition of H3.1/3.2 is presumably maintained at a low level to avoid the detrimental effect of K27me3 methylation on DNA replication in the paternal perinucleolar region.
Highlights
Heterochromatin, which is defined as transcriptionally inert and condensed chromatin, is heavily involved in the regulation of cellular processes such as gene expression, mitosis, and DNA replication (Campos & Reinberg, 2009; Saksouk et al, 2015)
The forced incorporation of H3.1 and H3.2 into the paternal pronucleus caused an increase in H3.1/2K27me3 and a delay in DNA replication in the perinucleolar region, leading to developmental failure. These results suggest that the nuclear configuration of H3 variants causes the asymmetric chromatin structure in parental pronuclei, and that reduced H3.1/2 nuclear deposition in the paternal perinucleolar region prevents accumulation of H3.1/2K27me3 modification, which has a detrimental effect on DNA replication
Inhibition of DNA replication by treatment of embryos with aphidicolin prevented the nuclear deposition of H3.1/2 in two-cell-stage embryos (Fig S2A), indicating that H3.1/2 is deposited into chromatin in a DNA replication–dependent manner during the two-cell stage, as in somatic cells (Tagami et al, 2004)
Summary
Heterochromatin, which is defined as transcriptionally inert and condensed chromatin, is heavily involved in the regulation of cellular processes such as gene expression, mitosis, and DNA replication (Campos & Reinberg, 2009; Saksouk et al, 2015). Pericentromeric heterochromatin can be identified microscopically as foci within the nuclear region that is densely stained with 49,6-diamidino-2-phenylindole (DAPI) In these regions, satellite repeats are transcriptionally silenced and DNA is late-replicating at the S phase (O’Keefe et al, 1992; Probst & Almouzni, 2011; Saksouk et al, 2015). Transcriptional activity of satellite repeats is higher and DNA replication is completed earlier, in paternal pericentromeric heterochromatin than in maternal heterochromatin (Aoki & Schultz, 1999; Puschendorf et al, 2008; Probst et al, 2010; Santenard et al, 2010). The mechanisms driving the structural and process-related differences between parental nuclei in pericentromeric heterochromatin have not been well characterized
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