Researchers at Sinai Health have made a surprising discovery about the role of DNA elements called transposons in early human development. Once considered to be rogue or harmful, the elements play a critical role in how embryos develop.
However, this new work challenges that assumption by providing clear evidence that transposons are essential for DNA normal embryonic development.
The study’s senior co-author Dr. Miguel Ramalho-Santos said, “People tend to think of transposons as akin to viruses, hijacking our cells. However, we found that those elements are not just genomic parasites. They are required in early development.”
The findings published in the journal Developmental Cell. The research focused on a type of transposon called LINE-1, for Long Interspersed Nuclear Element 1. While genes take up less than 2 percent of the genome, LINE-1 elements alone account for about 20 percent of our genetic material. Many scientists until recently had suspected that these jumping genes were potentially harmful because some of them can jump and copy themselves within the genome.
But this new study has flipped that view on its head. It shows that LINE-1 elements play a significant role during early development in humans. More precisely, they enable the forward progression of normal developmental stages in embryonic cells rather than causing regression.
Another senior author, Dr. Juan Zhang, found it perplexing that LINE-1 RNA messages were prevalent in early embryos. This suggested activity during the most tender phases of development. “If transposons are dangerous. Why are they active in early embryos?” Dr. Zhang asked.
To test this, Dr. Zhang switched off the expression of LINE-1 in cultured human ESCs. In doing so, these cells stepped back into an earlier stage where they became the same as one another and, therefore, could not develop further to form structures needed in the embryo. This experiment confirmed that LINE-1 was important to progress to later stages of development.
They found that LINE-1 elements participate in the arrangement of DNA within the nucleus. They ferry chromosomes, such as chromosome 19, for instance, to regions of gene repressors. This allows for proper differentiation of cells within the embryo-a kind of development across the board.
This could have major implications not only for fertility treatments but also for research into stem cells. It also opens up new avenues for understanding diseases like cancer. And neurological disorders, where LINE-1 plays a role.
Dr. Anne-Claude Gingras, Director of the LTRI, expressed excitement about the discovery: “This research breaks new ground in our understanding of human biology. I look forward to future discoveries from this work.”
ANI
