How moms and dads add something

A normal 4-day-old mouse embryo (L) and an embryo of the same age (parthenogenote) engineered to contain only maternal chromosomes. At this stage, the embryos (blastocysts) appear to be similar, but parthenogenote dies shortly, emphasizing the importance of inheriting the imprinted gene from both parents. Various cell types are stained green or red. Credit: Dr. Maki Asami.

Biologists at the University of Bath and the University of Vienna have discovered 71 new “imprinted” genes in the mouse genome. This brings us one step closer to unraveling some of the mysteries of epigenetics. This is a scientific field that explains how genes are turned on (off) in different cells, at different stages of development and adulthood.

Understand the importance of engraving gene To inherit, you need to take a step back and ask how inheritance works in general. Most of the 30 trillion cells in the human body contain genes from both the mother and father, and each parent provides one version of each gene. Unique combinations of genes are part of the way individuals are unique. Normally, each gene in a pair is equally active or inactive in a particular cell. This is not the case for imprinted genes. These genes make up less than 1% of the total of over 20,000 genes, but one parent version tends to be more active (and in some cases much more active) than the other.

So far, researchers have been aware of about 130 well-documented imprinted genes. Mouse genome— With new additions, this number will exceed 200.

“Imprint affects a key gene family that has a variety of effects on health and illness, so more than 70 new genes are available,” said Tony Perry, who headed research in the Department of Biology and Biochemistry in Bath, UK. Add important genes. Part of the jigsaw puzzle. “

Importance of histones

By scrutinizing the newly identified genes, Professor Perry and his colleagues were able to make a second important discovery. Switching the imprinted gene on and off is not necessarily associated with DNA methylation, where methyl groups are added to genomic DNA. It is known to suppress gene activity and turn them off). DNA methylation is the first known type of imprint, discovered about 30 years ago. From the results of the new research, it seems that the greater contribution to imprinting is made by histones, which are structures wrapped in genomic DNA of chromosomes.

Scientists have long known that histones act as “dimmer” switches in genes, fading off (or turning them back on), but until now, DNA methylation-imprinted gene activity. Was thought to provide the main switch for. The results of new research cast doubt on this assumption. Many of the newly identified genes have been found to be associated with changes in histone 3 lysine 27 (H3K27me3), with very few being associated with DNA methylation.

Why imprinting is important

Scientists have not yet figured out how to turn one parent version of a particular gene on or off (or fade it) and keep it that way when the other is in the opposite state. .. Many on / off switching is known to occur during gamete (sperm and egg) formation, but the exact mechanism remains unclear. This new study points to the interesting possibility that some imprinted genes may not be marked by gametes, but are activated late in development, or even in adulthood.

The proportion of genes is negligible, but imprinting is important in later life. If that doesn’t work and the imprinted gene copy from one parent is switched on when it should have been turned off (or vice versa), illness or death occurs. Incompletely imprinted genes are associated with many diseases, including neuropathy, metabolic disorders, and cancer.

“We may underestimate the relationship between imprinting and illness, and the relationship between imprinting and inheritance of parent-acquired illnesses such as obesity,” said Professor Perry. “Hopefully, this improved figure of imprinting will deepen our understanding. disease.. ”

Gene Silence – New Insights in Genomic Imprinting

For more information:
Laura Santini et al, Genomic imprinting of mouse blastocysts is primarily associated with H3K27me3. Nature Communications (2021). DOI: 10.1038 / s41467-021-23510-4

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University of Bath

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