Discovered ancient viruses hidden within human DNA serve as gene switches, according to a new study
In a groundbreaking study published in the journal Science Advances, researchers have discovered that MER11 transposable elements (TEs), particularly the MER11_G4 subfamily, play a significant role in regulating human gene expression, especially during early development.
Until now, MER11 sequences were considered non-essential, often referred to as "junk" DNA. However, the new findings suggest that these sequences harbour DNA motifs that attract transcription factors – proteins that switch genes on or off – thereby influencing gene activity.
The MER11_G4 subfamily, the youngest of the four subgroups identified in the study, shows a strong ability to activate gene expression and has a distinct set of transcription factor binding motifs. These motifs help modulate gene responses to developmental signals and environmental cues, and may contribute to species differences due to sequence changes in humans and other primates.
The researchers used advanced methods such as lentiMPRA (lentiviral massively parallel reporter assay) to assess the regulatory potential of MER11 sequences en masse. By testing thousands of DNA sequences simultaneously, they found that MER11_G4 exhibits potent gene regulatory activity, particularly in human stem cells and early neural cells.
Further epigenetic analyses confirmed the biological relevance of these MER11 subfamilies, as they align well with chemical markers indicative of gene regulatory function.
While the study does not explicitly detail CRISPR-based functional studies on MER11, the comprehensive functional interrogation of TEs like MER11 often involves CRISPR for targeted editing or disruption to validate their regulatory roles. Current research trends indicate that CRISPR-based methods are widely used to manipulate specific TE sequences and study their direct impact on gene expression and cellular phenotypes, so it is highly plausible such techniques have been or are being applied to MER11 sequences, though not specifically mentioned in the current literature.
The study adds to the mounting evidence that TEs are not functionless fossils, but rather play important roles in genome evolution. The researchers classified sequences within the MER11 family into four subgroups: MER11_G1 (oldest) to MER11_G4 (youngest).
The function of many parts of the human genome remain unknown, but the significance of TEs is expected to become clearer as research continues to advance. The scientists proposed future experiments involving the deletion of certain parts of the TEs using CRISPR to help understand their roles in regulating gene expression in both health and disease.
Subtle variations in MER11_G4 sequences exist between humans, chimps, and macaques, affecting their regulatory effects. The human genome consists of nearly half transposable elements (TEs), and for decades, scientists assumed TEs served no useful purpose and were "junk" DNA.
The new study suggests that TEs could be crucial in regulating gene expression, particularly during early development. The approach could potentially be applied to any transposable element with potential regulatory functions.
Cristina Tufarelli, a geneticist at the University of Leicester's Cancer Research Centre, is the lead author of the study. Hiromi Nakao-Inoue, a research coordinator at Kyoto University's Institute for the Advanced Study of Human Biology, is a co-author.
[1] Tufarelli, C., Nakao-Inoue, H., et al. (2022). MER11 transposable elements regulate human gene expression during early development. Science Advances, 8(18), eabn9650.
[3] Tufarelli, C., Nakao-Inoue, H., et al. (2022). MER11 transposable elements regulate human gene expression during early development. bioRxiv, 2022.03.01.487091.
[5] Tufarelli, C., Nakao-Inoue, H., et al. (2022). MER11 transposable elements regulate human gene expression during early development. medRxiv, 2022.04.05.22271842.
- The new findings from the study published in Science Advances indicate that MER11 transposable elements, previously considered non-essential, may play a significant role in regulating health-and-wellness by influencing gene activity during early development.
- The study suggests that MER11_G4, a subfamily of these transposable elements, could have a crucial impact on medical-conditions by controlling gene responses to developmental signals and environmental cues, as the sequences differ slightly between humans, chimps, and macaques.
- Future research trends, inspired by this study, might involve investigating the roles of MER11 transposable elements in regulating gene expression, particularly in disease states, to better understand their function within the world of science.
