Up until now, researchers thought that roughly 130 genes in the genome are imprinted genes—meaning that the maternal or paternal copy of the gene is marked so that it is expressed differently. Now, researchers have discovered 71 new “imprinted” genes in the mouse genome bringing the total number to over 200. This finding unravels some of the mysteries of how epigenetics controls processes such as embryonic development.
This work is published in Nature Communications, in the paper, “Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3.”
Usually, each gene in an inherited pair is equally active or inactive in a given cell. This is not the case for imprinted genes. These genes—which make up less than one percent of the total of 20,000+ genes—tend to be more active in one parental version than the other.
“Imprinting affects an important family of genes, with different implications for health and disease, so the seventy-plus new ones add an important piece of the jigsaw,” said Tony Perry, PhD, professor of mammalian molecular embryology at the University of Bath in the U.K.
Close examination of the newly identified genes allowed Perry and colleagues to make a second important discovery: the switching on and off of imprinted genes is not always related to DNA methylation, where methyl groups are added to genomic DNA. DNA methylation was the first known type of imprint, and was discovered around thirty years ago. Until now it was thought that DNA methylation provided the major switch for imprinted gene activity. The findings from the new study cast doubt on this assumption: many of the newly identified genes were found to be associated with changes to the histone 3 lysine 27 (H3K27me3), and only a minority with DNA methylation.
Scientists have yet to work out how one parental version of a given gene can be switched (or faded) on or off and maintained that way while the other is in the opposite state. It is known that much of the on/off switching occurs during the formation of gametes, but the precise mechanisms remain unclear. This new study points to the intriguing possibility that some imprinted genes may not be marked in gametes, but become active later in development, or even in adulthood.
Although it only involves a small proportion of genes, imprinting is important in later life. If it goes wrong, and the imprinted gene copy from one parent is switched on when it should be off (or vice versa), disease or death occur. Faulty imprinted genes are associated with many diseases, including neurological and metabolic disorders, and cancer.
“We may underestimate how important the relationship between imprinting and disease is, as well as the relationship of imprinting to the inheritance of parentally-acquired disease, such as obesity,” said Perry. “Hopefully, this improved picture of imprinting will increase our understanding of disease.”