DNA Methylation And Genomic Imprinting

Genomic imprinting is the biological process that turns genes on and off to help control early mammalian development as the embryo and placenta grow. Although errors in genomic imprinting can cause profound developmental defects and severe disorders that lead to lifelong health problems, neither the mechanisms behind genomic imprinting nor the errors that cause errors in the process are well understood.

Boston Children’s Hospital and Harvard Medical School scientists are working to remedy that shortcoming, and have identified a mechanism that regulates the process of gene imprinting in mice, including certain genes central to placental growth. Should the mechanism be confirmed via further research in humans, it is likely to offer a range of epigenetic therapies for various developmental disorders such as autism.

Image Credit: freepik

“Since its discovery over two decades ago, DNA methylation has been the only known mechanism governing genomic imprinting,” the study's first author and postdoctoral research fellow Azusa Inoue of the Harvard Medical School Department of Genetics said in a press release. “However, much to our surprise, the imprinted genes we looked at lacked DNA methylation, which told us there must be another mechanism at play.”

Easier Genetic Fixes

Researchers in this study noticed mysterious imprinted regions that were independent of DNA methylation as they were mapping parts of the genome in mouse embryos. In their hunt for patterns across the regions, they found a chemical modification to one of the histones — specifically, the consistent presence of H3K27me3. They then demonstrated that this histone modification was necessary for imprinting certain genes, in which DNA methylation played no role.

In total, the scientists identified 76 genes potentially regulated by H3K27me3 rather than DNA methylation. These imprinted genes are linked to severe eye anomalies, limb abnormalities, and issues with placental development, among other disorders. The study's results could lead to therapies for genetic imprinting defects. “A gene that is turned off by epigenetic modifications can be turned on much more easily than a gene that is mutated or missing can be fixed,” senior investigator and Boston Children’s/Harvard Medical School professor Yi Zhang said in the press release.

Share This Article