Brownian Motion of Interphase Chromatin in Living Cells

Wallace Marshall's project #2 in John Sedat's lab

Time-Lapse image of chromatin Brownian motion in living yeast cell

Large scale motion of chromatin is required in many essential biological processes, including meiotic homology search, recombination, chromosome condensation, and enhancer looping. In order to better understand the kinetics and mechanisms of these processes, I have directly measured the mobility of interphase chromatin in living cells in both yeast and Drosophila, by directly tracking the motion of defined chromosomal sites in vivo using 3D microscopy imaging of a green fluorescent protein construct (in yeast) or topoisomerase II (in Drosophila).

The result is that while chromatin does undergo diffusional motion at short time scales, at longer time scales this diffusion is constrained, which could reflect attachment of chromatin to the nuclear envelope or an internal nuclear skeleton. The diffusion constants measured are consistent with predictions of a reptation model given a high level of entanglement of chromosomes in the nucleus.

Current work is now focussing on two aspects of this work: (1) more about the physical basis of the motion - particularly the role of active processes in moving chromosomes and the nature of the confinement. (2) the biological ramifications of these results, particularly on homology searching and mating-type switching in yeast. The ultimate goal is to be able to relate the fundamental polymer physics of chromatin to the mechanism of essential processes in molecular biology. To stay posted, bookmark this page and check back often!

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