Chromosome dynamics and folding in eukaryotes: Insights from live cell microscopy

How chromosomes are folded and how this folding relates to function remain fundamental questions. Answering them is rendered difficult by the stochasticity of chromatin fiber motion which inevitably results in heterogeneity of the populations analyzed. Even if single cell analyses are beginning to yield precious insights, how can we determine whether a snapshot of position is related to function of the probed locus or cell-type? Fluorescence labeling of DNA at single or multiple loci allows determination of their position relative to nuclear landmarks and to each other, enabling us to derive physical parameters of the underlying chromatin fiber. Here I review the contribution of quantitative spatial and temporal analysis of labeled DNA to our understanding of chromosome conformation in different cell types, highlighting live cell imaging techniques and large scale geometrical analysis of multiple loci in 3D.