New gene silencing method discovered

US scientists have identified a new mechanism by which genes are silenced, or 'imprinted' during early embryonic development.

As imprinted genes are critical for early development, the discovery of this new epigenetic mechanism could have important implications for embryology research.

'Our discovery sheds new light on a fundamental biological mechanism and can lay the groundwork for therapeutic advances,' said Yi Zhang, a professor at HMS, Harvard Medical School, and Boston Children's Hospital and a Howard Hughes Medical Institute investigator, who led the research. '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.'

Embryos inherit two working copies of most genes from their parents, but for a small number of genes, one copy must be switched off for life in order to allow healthy development. This process is known as imprinting.

Prior to this discovery, the only mechanism that was known to function in genomic imprinting was DNA methylation, where genes are silenced by the attachment of chemicals called methyl groups to different parts of their DNA.

'Since its discovery over two decades ago, DNA methylation has been the only known mechanism governing genomic imprinting, said Dr Azusa Inoue of Harvard Medical School and first author on the paper. 'However, much to our surprise, the imprinted genes we looked at lacked DNA methylation, which told us there must be another mechanism at play.'

Researchers at Boston Children's Hospital and Harvard Medical School were mapping imprinted genes in developing mouse embryos when they discovered imprinted regions that lacked methylation. When they further investigated these methyl-independent regions, they found the common presence of modification to a histone - a bead-like protein which helps package DNA - called H3K27. When they removed the histone modifier from developing embryos, imprinting was lost – and both copies of the genes were expressed.

In total, the study identified 76 genes that were imprinted by histone modification. Importantly, many of these genes are linked to crucial developmental processes, including formation of the placenta, limb abnormalities and a disorder linked to eye development.

The study was published in Nature.