Discovered ancient viruses within our genetic makeup are responsible for turning genes on and off, according to a recent study.
In a groundbreaking study published in the journal Science Advances, researchers have shed light on the previously unknown functions of MER11 transposable elements (TEs) in regulating gene expression during early development.
Previously considered non-functional "junk" DNA, MER11 TEs are now understood to be dynamic, functional regulators of gene expression with critical roles during early developmental stages.
The study, led by a team of researchers including Hiromi Nakao-Inoue from Kyoto University's Institute for the Advanced Study of Human Biology and Cristina Tufarelli from the University of Leicester's Cancer Research Centre, focused on a specific family of TEs called MER11.
The researchers classified sequences within the MER11 family into four subgroups: MER11_G1, MER11_G2, MER11_G3, and MER11_G4. They found that the youngest members of the family, MER11_G4, have a strong ability to activate genes.
Subtle variations in MER11_G4 sequences exist between humans, chimps, and macaques, affecting their regulatory effect on genes. This suggests that these variations could play a role in primate speciation.
The function of many parts of the human genome remains unknown, according to Nakao-Inoue. However, the study provides evidence that TEs, such as MER11, play important roles in genome evolution and could be crucial in regulating gene expression.
The study used CRISPR, a gene-editing tool, to delete certain parts of the TEs and observe their effects on gene expression. Future experiments could involve deleting certain parts of the TEs to help unravel their roles in regulating gene expression in both health and disease.
The researchers found that MER11 elements harbor distinct transcription factor (TF)-binding motifs, allowing them to attract specific TFs that regulate nearby genes. This binding confers novel regulatory functions that evolved over time, influencing gene activity patterns crucial for early development.
Experimental evidence using massively parallel reporter assays (MPRA) has confirmed the regulatory potential of thousands of MER11 sequences, especially MER11_G4, supporting their functional role in primate gene regulation.
The patterns of chromatin accessibility and epigenetic markers like H3K27ac on MER11 elements correlate with active gene regulatory regions in human embryonic stem cells, reinforcing their role in developmental gene expression programs.
Overall, MER11 elements exemplify how TEs have been co-opted through evolution to serve as important "genetic switches," shaping gene regulatory networks during early human development.
The study's findings could have significant implications for our understanding of human development and genetics. As research continues to advance, the significance of TEs is expected to become clearer, potentially leading to new treatments and therapies for diseases related to gene expression.
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