Asymmetry in Histone H3 variants and lysine methylation between paternal and maternal chromatin of the early mouse zygote

Abstract

In mammalian fertilization, the paternal genome is delivered to the secondary oocyte by sperm with protamine compacted DNA, while the maternal genome is arrested in meiotic metaphase II. Thus, at the beginning of fertilization, the two gametic chromatin sets are strikingly different. We elaborate on this contrast by reporting asymmetry for histone H3 type in the pre-S-phase zygote when male chromatin is virtually devoid of histone H3.1/3.2. Localization of the histone H3.3/H4 assembly factor Hira with the paternal chromatin indicates the presence of histone H3.3. In conjunction with this, we performed a systematic immunofluorescence analysis of histone N-tail methylations at position H3K4, H3K9, H3K27 and H4K20 up to the young pronucleus stage and show that asymmetries reported earlier are systematic for virtually all di- and tri-methylations but not for mono-methylation of H3K4 and H4K20, the only marks studied present in the early male pronucleus. For H4K20 the expanding male chromatin is rapidly mono-methylated. This coincides with the formation of maternally derived nucleosomes, a process which is observed as early as sperm chromatin decondensation occurs. Absence of tri-methylated H3K9, tri-methylated H4K20 and presence of loosely anchored HP1-beta combined with the homogenous presence of mono-methylated H4K20 suggests the absence of a division of the paternal chromatin in eu- and heterochromatin. In summary the male, in contrast to female G1 chromatin, is uniform and contains predominantly histone H3.3 as histone H3 variant.

The double face of the histone variant H3.3

“…Notably, a major modification of the male gamete lies in the decondensation of the highly compacted protamine-containing sperm chromatin. Concomitant with protamine removal upon fertilization, nucleosomes containing H3.3, but not H3, are specifically assembled in paternal chromatin before the first round of DNA replication in Drosophila and in mouse [53][54][55]. The exclusive marking of paternal chromosomes with H3.3 in the zygote represents a primary epigenetic distinction between parental genomes and underlines an important consequence of critical and highly specialized function of H3.3 loading at fertilization.…”

“…The genome-wide enrichment of H3.3 at promoters and in the body of active genes is affected in HIRA knockout ES cells, suggesting a critical requirement for HIRA in H3.3 deposition at these specific regions (Figure 3) [24]. Moreover, HIRA is required for H3.3 deposition in the paternal chromatin during sperm nucleus decondensation upon fertilization in Drosophila and in mouse [53,54,61]. HIRA might also be involved in global H3.3 incorporation in the process of MSCI as HIRA level increases in the XY body concomitantly with H3.3 deposition [51].…”

Nuclear reprogramming: what has been done and potential avenues for improvements

“…The chromatin histone composition is central to this structure, with histone acetylation playing a major role in keeping such open chromatin conformation. Accordingly, both parental genomes (the paternal first) are loaded with acetylated H4K18 early in the zygote [63,64], probably to facilitate chromatin remodelling. Trichostatin A inhibits histone deacetylases (HDACs), conferring an open chromatin structure through histone hyperacetylation.…”

Asymétrie des génomes parentaux

“…ICR H19 [17]. Par ailleurs, d'autres travaux récents chez l'embryon précoce murin ont montré qu'une protéine appartenant à un complexe de remodelage de la chromatine, MBD3 [18], est impliquée dans le maintien de la méthylation au niveau de l'ICR paternel de H19.…”