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Morphogenesis of the genome during early development of C. elegans

Context. Genome and morphogenesis are not words that are usually found next to each other. The first one, genome, usually refers to dimensionless, textual information, whereas the second one, morphogenesis, brings to mind images of complex three-dimensional structures that change in size and shape over time. Nonetheless, and although it would be more correct to speak of chromatin morphogenesis, the unfamiliar combination applies well to one of the projects going on in the laboratory. Indeed, one of our goals is to determine how the genetic material folds into a complex three-dimensional shape in the cell nucleus. It is hypothesized that, analogous to what is found for proteins, 3D folding endows the genome with additional functions and creates an additional level of genetic information. In this view, the genome is considered to be an interconnected whole which adopts specific and reproducible structures, each of which might correspond to a given transcriptional program. Growing evidence does suggest that genome folding plays an important role in global gene regulation via the differential positioning of genes in the nucleus and their relationships to nuclear landmarks [1].

Goal and perspective. The goal is to identify reproducible patterns in the positioning of genes and chromatin segments during early development of C.elegans. The finding of such patterns would have profound implication for our understanding of genetic information. It would reveal an additional level of encoding in three dimensions. One provocative corollary could be that a given 3D structure corresponds to a given transcriptome, thereby opening the way for analysis of structure/function relationships at the level of the whole genome.

Methodology. The search for embryonic gene positioning patterns is performed using fixed cells and living cells. In the first case, multicolor 3D DNA FISH is combined with high-resolution confocal microscopy and image analysis to obtain spatial coordinates of key developmental loci which have similar expression patterns and ontology assignments. Loci are chosen based on the classification of genes made by Baugh et al. in an important study on the composition and dynamics of the C. elegans early embryonic transcriptome [2].

To analyze the spatial positioning and segregation of chromatin segments in living embryonic nuclei, a worm line expressing a photoconvertible fluorescent histone-fusion protein has been generated. This line is now being used to label specific nuclear subregions in vivo and to follow their behaviour and positioning throughout the cell cycle.