Helping mom make her mark

Chromosomal DNA, and the scaffolding of histone proteins that support it, both undergo chemical modification. For example, specialized enzymes might add or remove methyl chemical groups to modulate the expression of nearby genes.

A newly formed embryo receives genomic copies from each parent that differ considerably in their methylation profile and new research, from a team led by Toshinobu Nakamura and Toru Nakano of Osaka University, has revealed a protein with a critical role in maintaining these differences¹.

In the maternally contributed genome, many chromosomal segments contain a modification to histone 3, H3K9me2, which is essentially absent from the paternal genome. Experiments by Nakano and Nakamura showed that this is attributable to the PGC7 protein, which binds and shields these sites in the oocyte nucleus, while unprotected H3K9me2 sites get cleared away in the sperm-derived nucleus.

At the same time, PGC7 also prevents certain DNA modifications from taking place. In paternal chromosomal DNA, many 5-methylcytosine (5-mc) modifications get enzymatically transformed into 5-hydroxymethylcytosine (5-hmc), a change that markedly affects gene activity. The researchers determined that PGC7 binding prevents this change from happening to maternally contributed chromosomal DNA, ensuring that each parental genome copy is correctly ‘imprinted’, and that the right genes are switched on or off in each chromosome copy.