Post-mitotic chromatin remodelling during neuronal maturation
Once a neuron has been generated by a mitotic progenitor, it is post-mitotic and will not divide again. Relatively little is known about how the epigenetic state of the genome changes from a newly born neuron to a fully differentiated neuron. Furthermore, little is known about how these changes relate to the loss of cell fate plasticity during neuronal maturation. Cap-G (condensin subunit) and MEP-1 (NuRD complex) interact with Lola, a factor that prevents dedifferentiation of immature neurons. We have shown that knockdown of both Cap-G and MEP-1 specifically in neurons (from their birth onwards) results in developmental arrest and dramatic gene expression changes, including aberrant expression of genes that are not normally expressed in the developing brain. Furthermore, their genomic binding is highly dynamic during the maturation process.
Cap-G and MEP-1 both show significant overlap in binding with Lola in neurons, aligning with our hypothesis that Lola coordinates genome remodelling in this context. Continuing work includes determining whether Cap-G is acting with the whole condensin complex to remodel DNA topology, and how NuRD complexes are masking enhancers. These proposed lines of research will converge on a mechanistic understanding of how the neuronal genome is remodelled to restrict developmental plasticity.
Department of Life Sciences, Imperial College London
Génétique et biologie du développement (UMR3215 / U934)