Epigenetic reprogramming involving histone H3 variants, histone modifications and DNA methylation in mouse zygotes

摘要

In mouse zygotes, reprogramming involves chromatin reorganization and changes in the DNA modifications. The conversion of 5-methylcytosine (5mC) to 5-hydroxymethycytosine (5hmC) and further oxidized forms by the Tet dioxygenase 3 (Tet3) in maternal and maternal genomes has been associated to the modification status of histone H3 at lysine 9 (H3K9me2/3). It has also been shown that histone H3 variants H3.1, H3.2, H3.3, are asymmetrically and dynamically deposited into chromatin in DNA replication dependent and independent manner in the mouse zygote. Here we investigate the dynamics of H3 variants during epigenetic reprogramming in the zygote, in particular the control of H3K9me2 in relation to the phosphorylation status at H3S10 and H3T11 and their impact on changes in DNA modifications in mouse zygotes. We find that H3.1 and H3.2 are the prime targets for K9me2 modification impeding the oxidation of 5mC into 5hmC in an H3T11phos dependent manner in the maternal genome of mouse zygotes. Upon replication, K9me2 on both H3.1 and H3.2 is reduced and paralleled by a replication-dependent passive DNA demethylation in both parental genomes. For H3.3 we observe that phases of active DNA demethylation in both parental genomes are linked to distinct and unique dynamics of K9ac and T11phosphorylation, respectively. In summary our data indicate that a differential variant specific modification spectrum controls active and passive reprogramming processes in mouse zygotes.