April 26, 2017 Three drosophila epilines are shown. All share the same DNA sequence, but each has a unique eye color caused by transient perturbation of their epigenetic state. This perturbation alters levels of Polycomb-mediated repression of the eye color gene. Credit: Filippo Ciabrelli
Giacomo Cavalli's team at the Institute of Human Genetics (University of Montpellier / CNRS), in collaboration with the French National Institute for Agricultural Research (INRA), has demonstrated the existence of transgenerational epigenetic inheritance (TEI) among Drosophila fruit flies. By temporarily modifying the function of Polycomb Group (PcG) proteinswhich play an essential role in developmentthe researchers obtained fruit fly lines having the same DNA sequence but different eye colors. An example of epigenetic inheritance, this color diversity reflects varying degrees of heritable, but reversible, gene repression by PcG proteins. It is observed in both transgenic and wild-type lines and can be modified by environmental conditions such as ambient temperature. The scientists' work is published in Nature Genetics.
Same DNA, different color. Researchers have obtained drosophila epilinesthat is, genetically identical lineages with distinct epigenetic characteristicswith white, yellow, and red eyes respectively. They achieved this by transiently disturbing interactions between target genes and PcG proteins, which are complexes involved in the repression of several genes governing development. Cavalli and his team at the Institute of Human Genetics (University of Montpellier / CNRS) are the first to show that regulation of gene position can lead to transgenerational inheritance.
DNA is not the only medium for communicating information necessary for cell function. Cell processes are also determined by the chemical labeling (or marks) and specific spatial organization of our genomes, which are epigenetic characteristicsthat is, nongenetic but nonetheless inheritable traits. Epigenetic marks include modifications of histones, the proteins around which DNA is wound. PcG proteins, on the other hand, play a regulatory role by affecting 3-D chromosomal configuration, which establishes certain interactions between genes in the cell nucleus. The position of a gene at any given moment determines whether it is active or repressed.
Through temporary disruption of these interactions, the scientists were able to produce Drosophila epilines characterized by different levels of PcG-dependent gene repression or activation. They verified that these epilines were indeed isogenic, or genetically identical, by sequencing the genome of each. Despite their identical DNA, the integrity of epilinesand the unique phenotypic characteristics they programcan be maintained across generations. But this phenomenon is reversible. Crosses between drosophilas with over- or underexpressed genes and others having no such modifications to gene activity "reset" eye color without altering the DNA sequence, thus demonstrating the epigenetic nature of this inheritance.
The researchers then showed that new environmental conditions, such as a different ambient temperature, can affect the expression of epigenetic information over several generations, but they do not erase this information. Such transient effects of environmental factors to which earlier generations were exposed on the expression of characteristics in their progeny illustrate the unique, pliable nature of this epigenetic mechanism. By conducting "microcosm" experiments that recreated natural environmental conditions, the researchersworking with INRAconfirmed that epigenetic inheritance in Drosophila can be maintained in the wild.
Giacomo Cavalli's crew has therefore proven the existence of Polycomb-mediated stable transgenerational epigenetic inheritance dependent on 3-D chromosomal structure. Their findings offer new horizons for biomedical science. They suggest that epigenetics could partly solve the mystery of "missing heritability"that is, the absence of any apparent link between genetic makeup and certain normal hereditary traits and diseases.
Explore further: Biological mechanism passes on long-term epigenetic 'memories'
More information: Filippo Ciabrelli et al. Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila, Nature Genetics (2017). DOI: 10.1038/ng.3848
Journal reference: Nature Genetics
Provided by: CNRS
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