Ancient Viral Invasion Shaped Human Genome
ScienceDaily (Sep. 13, 2010) — Scientists at the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), and their colleagues from the National University of Singapore, Nanyang Technological University, Duke-NUS Graduate Medical School and Princeton University have recently discovered that viruses that 'invaded' the human genome millions of years ago have changed the way genes get turned on and off in human embryonic stem (ES) cells.
Scientists have discovered that viruses that "invaded" the human genome millions of years ago have changed the way genes get turned on and off in human embryonic stem cells. (Credit: iStockphoto/Martin McCarthy)
The study provides definitive proof of a theory that was first proposed in the 1950s by Nobel Laureate in physiology and medicine, Barbara McClintock, who hypothesized that transposable elements, mobile pieces of the genetic material (DNA), such as viral sequences, could be "control elements" that affect gene regulation once inserted in the genome.
This finding is an important contribution to the advancement of stem cell research and to its potential for regenerative medicine. Led by GIS Senior Group Leader Dr Guillaume Bourque, the study was published in Nature Genetics on June 6, 2010.
Through the use of new sequencing technologies, the scientists studied the genomic locations of three regulatory proteins (OCT4, NANOG and CTCF) in human and mouse embryonic stem (ES) cells. Interestingly, while the scientists found a lot of similarities, they also found many differences in the methods and the types of genes that are being regulated in humans. In particular, it was discovered that specific types of viruses that inserted themselves in the human genomes millions of years ago have dramatically changed the gene regulatory network in human stem cells.
"This study is a computational and experimental tour de force. It provides undeniable evidence that some transposable elements, which are too often dismissed as merely junk DNA, are key components of a regulatory code underlying human development," said Dr Cedric Feschotte, Associate Professor of the University of Texas Arlington.
Through the use of new sequencing technologies, the scientists studied the genomic locations of three regulatory proteins (OCT4, NANOG and CTCF) in human and mouse embryonic stem (ES) cells. Interestingly, while the scientists found a lot of similarities, they also found many differences in the methods and the types of genes that are being regulated in humans. In particular, it was discovered that specific types of viruses that inserted themselves in the human genomes millions of years ago have dramatically changed the gene regulatory network in human stem cells.
"This study is a computational and experimental tour de force. It provides undeniable evidence that some transposable elements, which are too often dismissed as merely junk DNA, are key components of a regulatory code underlying human development," said Dr Cedric Feschotte, Associate Professor of the University of Texas Arlington.
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NATURE GENETICS | LETTER
Transposable elements have rewired the core regulatory network of human embryonic stem cells
Galih Kunarso, Na-Yu Chia, Justin Jeyakani, Catalina Hwang, Xinyi Lu, Yun-Shen Chan, Huck-Hui Ng & Guillaume Bourque
Galih Kunarso, Na-Yu Chia, Justin Jeyakani, Catalina Hwang, Xinyi Lu, Yun-Shen Chan, Huck-Hui Ng & Guillaume Bourque
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Corresponding author
Nature Genetics 42 , 631–634 (2010) doi:10.1038/ng.600
Received 30 November 2009
Accepted 20 April 2010
Published online 06 June 2010
Erratum 13 June 2010
Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only ~5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.
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