The paper which came out of the MRC funded collaboration with Adrian Clark, Elia Stupka and others has finally been published in PlosOne after a fairly difficult gestation.
Genome-Wide Methylation and Gene Expression Changes in Newborn Rats following Maternal Protein Restriction and Reversal by Folic Acid
This paper describes the findings of genome wide assessment of DNA methylation assessed by MBD sequencing and whole genome microarray in a set of livers obtained from neonatal rats exposed to either control or low protein diets (with or without folate supplementation). We found differential expression of 618 genes at 5% FDR and 131 at 1% FDR associated with protein restriction. As with other microarray studies that we have performed, the main pathways affected were association with cell cycle regulation and DNA maintenance. Incredibly the folate supplementation removed all of these gene expression changes- a finding consistent with earlier work and strongly supporting the hypothesis that DNA methylation and availability of methyl donors plays a major role in programming. Protein restriction was associated with widespread differential methylation (1183 DMRs). Again, this effect was highly sensitive to folate availability. Surprisingly there was virtually no overlap between the DMR and gene expression differences, a finding that was difficult to explain.
In my view this is one of the most important papers that I have published. It offers some useful insight into the role of epigenetics in fetal programming. It confirms that the cell cycle plays a key role in the programming of tissue development and long-term health and that availability of folate is a modulator of the effects of protein undernutrition, emphasising that folate sufficiency in pregnancy is of critical importance for lifelong health.