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Epigenetics affects generations
"We saw indications of intergenerational inheritance of epigenetic information since the rise of epigenetic [studies] began in the early nineties. For instance, epidemiological studies reveal a striking correlation between the food supply of grandfathers and an increased risk of diabetes and cardiovascular disease in their grandchildren. Since then, various reports suggest epigenetic inheritance exists in different organisms. But molecular mechanisms [for transference] were unknown."
Iovino and his team at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany use fruit flies to explore how epigenetic modifications are transmitted from mother to embryo. Their recent study focused on a particular modification called H3K27me3 that can also be found in humans. H3K27me3 alters chromatin, the packaging surrounding DNA in the cell nucleus, and is mainly associated with repressing or "turning off" gene expression or function.
The Max Planck researchers found that H3K27me3 modifications that labeled chromatin DNA in the mother's egg cells, were still present in the embryo after it was fertilized even though other epigenetic marks had been erased. "This indicates that the mother passes on her epigenetic marks to her offspring. But we were also interested if those marks are doing something important in the embryo", explains Fides Zenk PhD, first author of the study.
The researchers then used a variety of genetic tools on fruit flies to remove the enzyme that attaches H3K27me3. They discovered that embryos lacking H3K27me3 during early development did not continue developing to the end of embryogenesis. Iovino: "It turned out that, in reproduction, epigenetic information is not only inherited from one generation to another, but is also important to development of the embryo itself".
Looking closer at the embryos, researchers found several important developmental genes, normally switched off during early embryogenesis, were turned on in embryos without H3K27me3. "We assume that activating those genes too soon during development disrupted embryogenesis and eventually caused the death of the embryo. It seems that inherited epigenetic information is needed to process and correctly transcribe the genetic code of the embryo", explains Fides Zenk PhD, Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics.
With these results, the study shows a clear biological consequence of inherited epigenetic information. Not only providing evidence that epigenetic modifications in flies can be transmitted across generations, but revealing how epigenetic marks transmitted from the mother can activate genes during early embryogenesis.
"Our study indicates that we inherit more than just genes from our parents. It seems we also get a fine-tuned as well as important gene regulation machinery that can be influenced by our environment and individual lifestyle. These insights can provide new ground for the observation that at least in some cases acquired environmental adaptations can be passed over the germ line to our offspring."
As the disruption of epigenetic mechanisms may cause diseases such as cancer, diabetes and autoimmune disorders, these new findings could have implications in human health.
Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of Polycomb repressive complex 2, is required for active propagation of H3K27me3 during early embryogenesis. H3K27me3 in the early embryo prevents aberrant accumulation of the active histone mark H3K27ac at regulatory regions and precocious activation of lineage-specific genes at zygotic genome activation. Disruption of the germ line–inherited Polycomb epigenetic memory causes embryonic lethality that cannot be rescued by late zygotic reestablishment of H3K27me3. Thus, maternally inherited H3K27me3, propagated in the early embryo, regulates the activation of enhancers and lineage-specific genes during development.
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Egg-cell of a female fruit fly [WHITE ARROW] in which H3K27me3 was made visible by green stain.
This egg cell fused with a sperm, will form one of the next generation of flies. In the upper right corner,
a maternal and paternal pre-nucleus are depicted before fertilization. The green color of H3K27me3
appears exclusively in the maternal pre-nucleus, indicating epigenetic instructions are inherited
into the next generation. Image credit: MPI of Immunobiology a. Epigenetics/ Fides Zenk PhD