Research

We are interested in the interplay between transposable elements and the host genome at the level of transcriptional regulation

Courtesy: National Science Foundation

Transposable elements (TEs) are a highly diverse group of genetic entities that can move around the genome, although they may lose that capacity through mutational processes. On one hand, TEs pose a mutagenic risk to their host, such that their activity needs to be restricted by transcriptional silencing and other mechanisms. On the other hand, TEs are a source of coding and non-coding sequences that can be co-opted by the host to drive evolution. Our lab aims to understand how mechanisms of transcriptional regulation are involved in these two seemingly opposing facets of transposon biology, as well as their impact on the host. We mainly focus on early mammalian development.

Control of TE expression

In most somatic tissues, TEs are transcriptionally repressed by a variety of mechanisms, including DNA methylation and histone modifications. We aim to better understand these mechanisms, and are particularly interested in cases where the epigenetic landscape is distinct to that seen in most somatic tissues, such as during preimplantation development. Past work from the lab in this area focused on the role of the DNA demethylating TET enzymes in mouse embryonic stem cells (de la Rica et al, 2016; Deniz et al, 2018). We are also developing epigenomic methods that deal with the repetitiveness of TEs.

TEs as gene regulators

Non-coding sequences within TEs harbour multiple binding sites for host transcription factors. As TEs spread throughout the genome, some of these sequences can become important regulators of host gene expression. We aim to establish causal links between TE regulatory capacity, gene expression and phenotypes. To date, we have undertaken studies in mouse embryonic and trophoblast stem cells (Todd et al., 2019), and in the context of acute myeloid leukemia (Deniz et al., 2020).

TEs in placental evolution

Credit: The Placenta Rainbow : immune system regulation of placental development, mouse.  Attribution 4.0 International (CC BY 4.0)

Our lab has a long-standing interest in placental transcriptional regulation (e.g., Branco et al., 2016; Schoenfelder et al., 2018). The unique epigenetic landscape of the placenta presents an apparently permissive environment for TE expression, which may have led to an extensive co-option of TEs as placental genes and regulatory elements. We started dissecting the contribution of TEs to the enhancer landscape of mouse trophoblast (Todd et al., 2019), and are continuing this work, as well as extending it to primates.

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