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<a rel = "lightbox" href = "https://3c1703fe8d.site.internapcdn.net/newman/gfx/news/2019/3-newstudyshow.jpg" title = "In these pages C. elegans embryos, only the chromosomes inherited from the egg are colored green. All chromosomes are stained red for DNA. By distinguishing between the chromosomes inherited from eggs and spermatozoa, the researchers were able to follow the effects of the epigenetic marks carried by the chromosomes of spermatozoa. Credit: K. Kaneshiro ">
In these C. elegans embryos, only the chromosomes inherited from the egg are colored green. All chromosomes are stained red for DNA. By distinguishing between the chromosomes inherited from eggs and spermatozoa, the researchers were able to follow the effects of the epigenetic marks carried by the chromosomes of spermatozoa. Credit: K. Kaneshiro
When an organism develops and reacts to its environment, the genes in its cells switch on and off constantly, with different patterns of gene expression in different cells. But can changes in gene expression be pbaded from parents to their children and to subsequent generations? Although the indirect evidence of this phenomenon, called "transgenerational epigenetic inheritance", is increasing, they remain controversial because their mechanisms are so mysterious.
Researchers at the University of Santa Cruz have now shown that epigenetic information carried by parental sperm chromosomes can lead to changes in gene expression and development of offspring. Their study, published on March 20 in Nature Communications, involved a series of intelligent experiments using the nematode worm Caenorhabditis elegans.
Epigenetic changes do not alter the gene's DNA sequences, but rather involve chemical modifications either of the DNA itself, or of the histone proteins with which the DNA is encapsulated in the chromosomes. These modifications or "marks" change the expression of genes, activating or deactivating genes.
In their experiences with C. elegans, researchers at Susan Strome's laboratory at the University of Santa Cruz focused on histone markings, the specific amino acid modifications in the tail of histone proteins. Strome, professor of molecular, cellular and developmental biology, said the new study addressed a central issue in the field of epigenetics.
"It's a very direct question: does the inheritance of sperm chromosomes with a modified packaging of histone in DNA affect the expression of genes in the offspring? And the answer is yes, "she said.
The first author, Kiyomi Kaneshiro, a graduate student from Strome's lab who led the study, said C. elegans It is a good model to study this question because the conditioning of the histones is entirely retained in the sperm chromosomes of the worm. In humans and other mammals, histone conditioning is only partially retained in sperm.
"There is a debate about the amount of histone packaging kept in humans, but we know that it is conserved in some areas of the genome important for development," he said. Kaneshiro.
Researchers have focused on epigenetic transmission in the paternal line because sperm contributes little more than its chromosomes to the embryo. The egg contains many other components that can influence the development of the embryo, making it more difficult to determine the epigenetic effects in the maternal line.
In his experiments, Kaneshiro selectively removed a specific histone mark from the sperm chromosomes, then fertilized the eggs with the modified sperm and studied the resulting offspring. A crucial innovation was to use sperm and eggs from two different strains of C. elegans, which allowed Kaneshiro to distinguish chromosomes inherited from sperm from those inherited from the ovum. She chose strains of worms originating in Britain and Hawaii that evolved separately long enough to accumulate many small genetic differences (called single nucleotide polymorphisms).
"The fathers were British and the mothers were Hawaiian, and there are enough differences between them so that we can distinguish the two parental genomes in the cells of their offspring," said Kaneshiro. "Through this hybrid system, we could see differences in gene expression that resulted directly from changes in histone markings on sperm chromosomes."
In addition, these changes in gene expression have developmental implications. With the elimination of histone markings, sperm chromosomes have lost a repressive signal that normally prevents certain genes from remaining active in the germline of the offspring (the cells that give rise to eggs and sperm) . Kaneshiro observed that the germ cells of the offspring activated the neuronal genes and began to develop into neurons.
The particular histone mark removed in these experiments is a widely studied epigenetic mark, found in animals, ranging from worms to fruit flies, to humans. "This mark is found on histones that are conserved on sperm chromosomes in humans," Kaneshiro said.
New discoveries show that hereditary epigenetic marks affect the expression and development of genes. But the study involved artificially modifying the marks on sperm chromosomes. What remains to be understood is how the environmental effects on an adult organism could alter the epigenetic marks in its germ cells, thus allowing these environmental effects to be pbaded on to subsequent generations.
"Our results raise the possibility that histone marks are vectors of transgenerational epigenetic inheritance," Kaneshiro said. "We know that the environment in which an organism lives can alter patterns of gene expression in somatic cells [non-germline body cells]. If this modifies patterns of gene expression in the germ line, we expect these changes to be inherited, but we have not yet shown it. "
Explore further:
Study documents paternal transmission of epigenetic memory via sperm
More information:
Nature Communications (2019). DOI: 10.1038 / s41467-019-09141-w
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