Amazing stuff!
"... The study focused on a group of transposable elements (TEs) embedded in the human genome.
TEs are repetitive DNA sequences that originated from ancient viruses. These genes can “jump” around and change their position on a chromosome.
After their discovery in 1983 by Barbara McClintock, TEs were thought to have no known biological function, earning them the nickname junk DNA. ..."
"... the researchers developed a new method for classifying TEs. Instead of using standard annotation tools, they grouped MER11 sequences based on their evolutionary relationships and how well they were conserved in the primate genomes.
This new approach allowed them to divide MER11A/B/C into four distinct subfamilies, namely, MER11_G1 through G4, ranging from oldest to youngest.
This new classification revealed previously hidden patterns of gene regulatory potential. ...
To directly test whether MER11 sequences can control gene expression, the team used a technique called lentiMPRA (lentiviral massively parallel reporter assay). This method allows thousands of DNA sequences to be tested at once by inserting them into cells and measuring how much each one boosts gene activity.
The researchers applied this method to nearly 7,000 MER11 sequences from humans and other primates, and measured their effects in human stem cells and early-stage neural cells.
The results showed that MER11_G4 (the youngest subfamily) exhibited a strong ability to activate gene expression. It also had a distinct set of regulatory "motifs," which are short stretches of DNA that serve as docking sites for transcription factors, the proteins that control when genes are turned on. These motifs can dramatically influence how genes respond to developmental signals or environmental cues. ..."
From the abstract:
"Current approaches for classifying and annotating endogenous retroviruses (ERVs) and their long terminal repeats (LTRs) have limited resolution and are inaccurate. Here, we developed an annotation approach based on phylogenetic analysis and cross-species conservation. Focusing on the evolutionarily young LTR subfamilies known as MER11A/B/C, we revealed the presence of four “new subfamilies,” suggesting a new annotation for 412 (19.8%) of these repeat elements. We then validated their regulatory potential using a massively parallel reporter assay.
We further identified motifs associated with their differential activities including an ape-specific gain of SOX-related motifs through a single-nucleotide deletion. By applying our approach across 53 simian-enriched LTR subfamilies, we defined 75 new subfamilies and found a novel annotation for a total of 3807 (30.0%) instances from 26 subfamilies. With this refined annotation of simian-enriched LTRs, it will be possible to better understand the evolution in primate genomes and potentially identify critical roles for ERVs and their LTRs in the hosts."
A phylogenetic approach uncovers cryptic endogenous retrovirus subfamilies in the primate lineage (open access)
Fig. 2. MER11 new subfamilies display more consistent epigenetic profiles as compared to original annotations.
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