Transposable elements (TEs) are mobile genetic
entities that are present by millions in mammalian genomes. Their effects are
pleiotropic, from insertional mutagenesis to chromatin position effects or
chromosome rearrangements. While TEs have prompted useful innovations during
evolution, they constitute a genomic threat in the short term. Accordingly,
cells use several strategies to tam TEs, among which DNA methylation plays a
key role. Importantly, TE activity has been linked to several diseases,
including cancer and infertility. Notably, our team previously showed that
meiosis is particularly vulnerable to TE activity: when TEs fail to be
repressed during male germline development, homologous chromosome pairing is
impaired at meiosis, leading to spermatogenesis interruption and male sterility.
The project aims at deciphering the
relationship between TEs and meiosis, using two unique mouse models of TE
reactivation, resulting from deficient DNA methylation or from temporally
controlled CRISPR-based activation. Innovative genomic, bioinformatic and
microscopy approaches will be carried out to:
1) investigate the impact of TE activity
on the meiotic chromatin landscape and distribution of recombination sites,
2) investigate the impact of TE activity
on meiotic chromosome conformation
3) control in space and time TE
reactivation during meiosis.
We hope to
uncover how TEs influence chromosome integrity, with broad implications for
reproductive and cancer research.