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!
PublicationMarshall WF, Straight A, Marko JF, Swedlow J, Dernburg A, Belmont A, Murray AW, Agard DA, and Sedat JW. 1997. Interphase chromosomes undergo constrained diffusional motion in living cells. Current Biology 7,930-939.
Other Information:Science News article discussing this work
Read more about chromatin-NE interactions
Our efforts to study chromosome mechanics during mitosis