Transcriptional silencing is important to prevent expression of transposable elements
that may deregulate the genome once activated. Broadly, transcriptional silencing
involves local modifications of the composition of chromatin to a specialized silencing
form called heterochromatin. However, the mechanisms that target the deposition of
heterochromatin remain unclear. The chromatin remodeler Decreased DNA Methylation
1 (DDM1) was identified 25 years ago as a main controller of transposon silencing and
more recently was shown to deposit heterochromatin. Most chromatin remodelers
function as protein complexes but DDM1 has remained exceptional by the absence of
interacting proteins that could form a complex and target DDM1 to transposable
elements.
The objective of this proposal is to identify proteins forming a DDM1 complex including
trans-acting factors that could target DDM1 to transposable elements.
Two main research axes are proposed: a genetic screen and proximity labelling. These
will identify direct interactors of DDM1 and a combination of genetics, genomics and
biochemistry will establish the role of DDM1 interactors in silencing transposable
elements.
DDM1 is the major pathway silencing transcriptionally TEs in plants. The identification of
trans-acting DDM1 interactors would provide means to engineer new targeted
transcriptional silencing strategies in crops. This form of silencing could be epigenetically
inherited across generations in absence of the initial targeting event. DDM1 orthologs in
mammals are involved in prevention of severe epigenetic disorders. The trans-acting
interactors of DDM1 might show a strong degree of conservation in mammals and be of
interest for targeting pharmacological agents.