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2016 ; 110
(10
): 2162-8
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Chromosome Compaction by Active Loop Extrusion
#MMPMID27224481
Goloborodko A
; Marko JF
; Mirny LA
Biophys J
2016[May]; 110
(10
): 2162-8
PMID27224481
show ga
During cell division, chromosomes are compacted in length by more than a
100-fold. A wide range of experiments demonstrated that in their compacted state,
mammalian chromosomes form arrays of closely stacked consecutive ?100 kb loops.
The mechanism underlying the active process of chromosome compaction into a stack
of loops is unknown. Here we test the hypothesis that chromosomes are compacted
by enzymatic machines that actively extrude chromatin loops. When such
loop-extruding factors (LEF) bind to chromosomes, they progressively bridge sites
that are further away along the chromosome, thus extruding a loop. We demonstrate
that collective action of LEFs leads to formation of a dynamic array of
consecutive loops. Simulations and an analytically solved model identify two
distinct steady states: a sparse state, where loops are highly dynamic but
provide little compaction; and a dense state, where there are more stable loops
and dramatic chromosome compaction. We find that human chromosomes operate at the
border of the dense steady state. Our analysis also shows how the macroscopic
characteristics of the loop array are determined by the microscopic properties of
LEFs and their abundance. When the number of LEFs are used that match
experimentally based estimates, the model can quantitatively reproduce the
average loop length, the degree of compaction, and the general loop-array
morphology of compact human chromosomes. Our study demonstrates that efficient
chromosome compaction can be achieved solely by an active loop-extrusion process.
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