SUV4-20 activity in the preimplantation mouse embryo controls timely replication

The figure shows a normal embryo (top two panels) and an embryo with additional expression of SUV4-20 (bottom two panels, methylation shown in red). Source: Helmholtz Zentrum München/Andre Eid.

Extensive chromatin remodelling is thought to occur after fertilisation and be necessary to allow a new developmental programme to begin.  This remodelling includes dynamic changes in histone methylation, including remodeling of constitutive heterochromatic marks such as histone H4 Lys20 trimethylation (H4K20me3).  In this study, the role of H4K20 methylation states through the action of the SUV4-20 methyltransferases is addressed. Suv4-20h1/h2 are shown to be mostly absent in mouse embryos before implantation, underscoring a rapid decrease of H4K20me3 from the two-cell stage onwards. Ectopic expression of Suv4-20h2 in early embryos leads to sustained levels of H4K20me3, developmental arrest, and defects in S-phase progression. This developmental phenotype can be partially overcome through inhibition of the ATR pathway, suggesting that the main function for the remodeling of H4K20me3 after fertilization is to allow the timely and coordinated progression of replication. This is in contrast to the replication program in somatic cells, where H4K20me3 has been shown to promote replication origin licensing, and anticipates a different regulation of replication during this early developmental time window.

Original publication: Eid, A. et al. (2016) SUV4-20 activity in the pre-implantation mouse embryo controls timely replication. Genes and Development, doi: 10.1101/gad.288969.116

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