Chromatin folding: from linear chromosomes to the 4D nucleus

The organization of chromatin within the nucleus influences gene expression during cell differentiation and development. Recent work took advantage of the genome-wide localization of molecular marks on chromosomes to analyze their linear distributions at different length scales. Moreover, chromosome conformation capture techniques detect spatial proximity inside the cell nucleus and allow us to characterize local and long-range chromatin loops as well as interchromosomal contacts. These techniques have improved our understanding of chromatin composition in eukaryotic chromosomes, but the principles governing nuclear organization are still little understood. On the one hand, proteins might localize in stable nuclear structures, such as transcription factories, on which chromatin would have to be targeted to be processed. On the other hand, proteins binding to chromatin might induce the formation of specialized nuclear compartments de novo. Current work is aimed at distinguishing between these possibilities and at elaborating predictive models of chromatin folding.