Humans have developed elaborate systems such as script, books, computers and virtual networks to ensure that knowledge is preserved throughout multiple generations. Researchers led by Ester Baart at Erasmus MC in the Netherlands wanted to understand and uncover other mechanisms – in particular those developed by cells to preserve their epigenetic knowledge over generations.
Owing to the heavy compaction of the sperm DNA by incorporation of protamines the paternal and maternal genomes in the mammalian zygote exist in an asymmetric configuration. Some of this asymmetry needs to be retained in order to maintain parental imprinting, while at other chromatin domains, such as constitutive heterochromatin (cHC), epigenetic symmetry needs to be reestablished.
The latter has been studied mainly during mouse preimplantation development where the paternal genome is largely devoid of canonical cHC marks including HP1-bound trimethylated histone H3K9 (H3K9me3) and reestablishment is achieved de novo via a polycomb repressive complex 1/2 (PRC1/2)-dependent intermediate.
However, little is known about how this process is regulated during human embryogenesis and therefore van de Werken et al. set out to shed some light onto this crucial moment during human development.
Here is what they found:
- In contrast to mouse zygotes, human pronuclei already exhibit DAPI dense regions similar to those found in somatic cells.
- PRC1/2 are not associated with paternal chromatin during cleavage stages probably due the absence of active PRC1/2 complexes.
- In humans paternal chromatin is marked by H3K9me3 at DAPI-rich regions, particularly on satellite DNA repeats.
- Human sperm contributes already H3K9me3 marked histones to the zygote, which is then recognized and maintained by the maternal H3K9/HP1 pathway.
With this, the researchers conclude that human embryos exhibit intergenerational epigenetic inheritance of the cHC structure, which is directly passed on from the paternal, sperm-derived epigenome.
To profit from this example of digitally conserved knowledge have a look at Nature Communications, December 2014 for all the details.