Abstract
BackgroundIn the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of histone H3 variants and distinct patterns of DNA and histone modifications. The molecular mechanisms linking histone variant-specific modifications and DNA methylation reprogramming during the first cell cycle remain to be clarified.ResultsHere, we show that the degree and distribution of H3K9me2 and of DNA modifications (5mC/5hmC) are influenced by the phosphorylation status of H3S10 and H3T11. The overexpression of the mutated histone variants H3.1 and 3.2 at either serine 10 or threonine 11 causes a decrease in H3K9me2 and 5mC and a concomitant increase in 5hmC in the maternal genome. Bisulphite sequencing results indicate an increase in hemimethylated CpG positions following H3.1T10A overexpression suggesting an impact of H3S10 and H3T11 phosphorylation on DNA methylation maintenance.ConclusionsOur data suggest a crosstalk between the cell-cycle-dependent control of S10 and T11 phosphorylation of histone variants H3.1 and H3.2 and the maintenance of the heterochromatic mark H3K9me2. This histone H3 “phospho-methylation switch” also influences the oxidative control of DNA methylation in the mouse zygote.
Highlights
In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications
H3S10phos and H3T11phos have different dynamics and associations with histone H3 variants in the mouse zygote We first determined the dynamics of H3S10phos and H3T11phos in the developing mouse zygotes
H3T11phos accumulates in the perinucleolar heterochromatin but follows a different dynamic: it is absent in G1, becomes first visible during early S-phase and gradually accumulates during S-phase to remain as a strong signal up to G2 (Fig. 1)
Summary
Epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The epigenetic reprogramming in mouse zygote involves an extensive rearrangement of the epigenetic landscape, including chromatin reorganization and comprehensive changes in DNA modifications. These changes require a coordinated control of epigenetic “writers”, “readers”, “erasers” and “remodelers” on the level of histones and DNA after fertilization. We analyse the synergetic dynamics of different post-translational modifications in histone H3 variants H3.1, H3.2 and H3.3 which are found in different epigenetic compartments of chromatin [1] As a consequence of this, the maternal chromosomes appear to maintain 5mC levels in contrast to the more oxidized paternal chromosomes, which are practically devoid of H3K9me at early stages of DNA replication and where 5mC is extensively converted to 5hmC by Tet, reducing DNA methylations by about 50% at the end of the first cell cycle [10]
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