Activity of human retrotransposons in cultured cells, developing embryos and the germline
L1 or LINE-1 retrotransposons are the “master” transposons in the human genome, providing the machinery required to mobilise not only themselves, but also non-autonomous transposons and even human genes. Understanding when and where these molecular parasites move has profound implications for their impact on human genome evolution. Recent studies have shown that while most transposons restrict their activity to the germline L1 retrotransposons may specifically target the early stages of development. We use genome-wide analyses, both in the lab and in silico to investigate the dynamics and regulation of this unusual behaviour, in cultured human cells and DNA from embryonic and germline sources.
Analysis of chimpanzee specific active retrotransposons
In collaboration with Twycross Zoo (The World Primate Centre)
we are developing tools to study the activity of L1 retrotransposons
in our closest living relative: the chimpanzee.
Chimpanzees at Twycross have been trained, as part of their enrichment and health care regimen, to allow collection of DNA by mouth swabs.
These samples, obtained in a stress-free manner, are underpinning
our exploration of L1 diversity and activity in chimpanzees.
Genome dynamics and regulation of mouse IAP retrotranspons
IAP elements are virus-like transposons that cause a significant proportion of mutations in laboratory mice, by jumping into and disrupting essential genes. Their activity is strongly regulated by epigenetic changes, and sometimes their regulatory sequences are co-opted to drive mouse gene expression.
As such IAP transposons can be used as reporters of genome-wide epigenetic alterations, such as those that often occur in cancer.
Conversely by studying manipulations of mouse epigenetic marks they can become a model system to examine how transposon activity is regulated.