A bright day with some bright ideas
Transposable elements (TEs) are repetitive DNA sequences able to ‘jump’ in the host genome. They contribute to genome plasticity and evolution in many different ways, by bringing new regulatory sequences in the vicinity of genes or by generating chromosomal rearrangements. They are found in all sequenced organisms to date, and represent a variable proportion of the genomes: from only 3% in yeast to 45% in human and more than 85% in maize and wheat.
For a long time TEs were considered as junk DNA, without biological function besides the harmful effects they generate. In the last years, there has been an explosion of interest for TEs and their functions in the genome.
The 3rd International Congress on Transposable Elements (ICTE) in Saint-Malo (France) has illustrated this shift in focus. From the 16th to the 19th of April 2016, a bright sunshine welcomed more than 150 researchers, engineers and students from all over the world to share their knowledge on TEs in bacteria, fungi, animals and plants, through numerous talks and posters.
What was talked about?
Sir David Baulcombe gave an overview of the evolution and the central role of small RNAs in transgenerational silencing pathways of TEs in plants
ICTE 2016 started off strong with a presentation by Sir David Baulcombe, who gave an overview of the evolution and the central role of small RNAs in transgenerational silencing pathways of TEs in plants, notably in tomato.
This introduction highlighted the importance of TEs in adaptive processes and during the meeting, the positive evolutionary impact of TEs was discussed in a broad range of species. In mammals, Cédric Feschotte has shown how TEs participate in remodeling the genome and acquiring new adaptive roles for the host.
His lab has demonstrated that endogenous retroviruses (HERVs) in the human genome are able to bind STAT1, an effector of the interferon (IFN) pathway, involved in immune responses. The enrichment of HERVs in IFN-activated genes suggests their role as enhancers of gene expression and, consequently, their implication in the regulation of essential immune system genes.
Furthermore, Henry Levin presented an example of the yeast retrotransposon Tf1 which, in response to environmental changes, targets the promoter region of stress response genes. Indeed, in presence of cobalt, a toxic metal known to induce DNA damage, Tf1 activity is greatly increased leading to a transcriptional up-regulation of genes involved in the TOR pathway, and thus conferring resistance to such stress.
The star of the show was undeniably LINE-1 (L1), one of the three families of mobile elements still active in humans.
The star of the show was undeniably LINE-1 (L1), one of the three families of mobile elements still active in humans. The activity of L1 is well known and the downstream effects of this activity were discussed.
Geoffrey J. Faulkner presented a single-cell retrotransposon capture sequencing analysis (RC-seq) and showed evidence that L1, usually heavily inhibited after embryogenesis in all cells, can be mobilized in hippocampal and cortical neurons, contributing to cell mosaicism. He suggested that L1 are potentially involved in building and fine-tuning neuronal networks.
Didier Trono indicated that specific transcription factors KRAB-ZFPs bind to TEs, which can behave as tissue-specific enhancers and regulate their transposition in human embryonic stem cells as well as in adult tissues leading to a KRAB-ZFP-mediated differentiation. Together, these transcriptional factors and TEs partner up to play major roles in the specification and evolution of several species including humans. These two examples beautifully illustrated TE implication not only in intergenerational diversity, but also between cells of the same organism.
Uncovering the evolutionary history
Another aspect highlighted during the congress was about how TEs contribute to the evolution of a species. Leandro Quadrana showed of how genome-wide association studies (GWAS) can be utilized in investigating transpositional movements throughout an evolutionary history.
It appears that in the Arabidopsis genome, a huge part of TEs had contributed to new insertions in recent history.
It appears that in the Arabidopsis genome, a huge part of TEs had contributed to new insertions in recent history. In addition, the transposition activity of TEs varied between different accessions of Arabidopsis thaliana and could be linked to environmental and genetic factors. This highlighted the impact of the mobilome in the genetic diversity observed in one species.
Continuing on from this, Olivier Panaud presented the role of TEs in the variation of genome sizes in plants. He had analyzed the transpositional history in Oryza species over 15 million years of evolution pointing out not only the new insertions due to TEs but also their elimination rate, bringing to light a striking picture of TE turn-over during evolution. This kind of analysis represents the future challenge in better understanding how TEs shape eukaryotic genomes and further identifying the fundamental roles of TEs in adaptive evolution.
The non-self-recognition systems found in prokaryotes have led to many new applications in the field of applied biology. In particular, the CRISPR-Cas system discovery by Emmanuelle Charpentier was one of the major breakthroughs in recent history that has been very well illustrated at the ICTE 2016.
This mechanism discovered in bacteria has led to a revolution in science as it represents a powerful genome engineering technology opening the door to a process that has long been thought of as almost impossible; the CRISPR-Cas system allows to target and modify very precise DNA sequences in vivo.
Another breakthrough process, presented by Zoltán Ivics, takes command of Sleeping Beauty, a DNA transposon involved in improving gene-delivery therapies.
Another breakthrough process, presented by Zoltán Ivics, takes command of Sleeping Beauty, a DNA transposon involved in improving gene-delivery therapies. These trials, which use modified viruses to deliver genes to patients, started in 2000 but have only been semi-successful due to the integration selectivity of the retroviral vectors, which often target actively transcribed units, therefore activating proto-oncogenes and leading to cancers.
Sleeping Beauty is an interesting solution to this problem; it integrates in a close to random fashion, but knowing that only 1% of the human genome is composed of coding sequences the risk of deleterious integration is very low. The consensus here was that the world is opening up to a new era of TE-based gene therapies.
Academic rigor and research excellence
After 4 sunny days of intense exchanges between guests of honor, researchers and PhD or postdoctoral fellows, the congress wrapped up. The TE community is strengthened by its diversity and the organizers of ICTE 2016 had succeeded to combine academic rigor and research excellence with conviviality. We would like to extend thanks to all the organizers and participants of the ICTE 2016 and we hope to see you again at ICTE 2020.
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