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Self-organization of domain structures by DNA-loop-extruding enzymes.

Alipour E, Marko JF - Nucleic Acids Res. (2012)

Bottom Line: If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained.The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines.This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

View Article: PubMed Central - PubMed

Affiliation: Center for Cell Analysis and Modeling, University of Connecticut Health Sciences Center, Farmington, CT 06030, USA. elnaz.alipour@gmail.com

ABSTRACT
The long chromosomal DNAs of cells are organized into loop domains much larger in size than individual DNA-binding enzymes, presenting the question of how formation of such structures is controlled. We present a model for generation of defined chromosomal loops, based on molecular machines consisting of two coupled and oppositely directed motile elements which extrude loops from the double helix along which they translocate, while excluding one another sterically. If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained. However, if dissociation and rebinding of the machines occurs at a finite rate (finite processivity), the steady state qualitatively changes to a highly ordered 'stacked' configuration with suppressed fluctuations, organizing a single large, stable loop domain anchored by several machines. The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines. Possible realizations of these types of molecular machines are discussed, with a major focus on structural maintenance of chromosome complexes and also with discussion of type I restriction enzymes. This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

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Loop-size distribution for M = 5 pairs of non-disassociating loop-extruding machines on a lattice of size L = 50. The probability distribution broadens as the bias () increases. Main figure shows results for  1.05 (dot-dashed line), 1.5 (dashed line) and 4.0 (solid line). Inset: comparison of steady-state loop-size distributions for exact statistical theory (solid black line) and kinetic simulation  (gray bars); difference between them is negligibly small. The simulation was run  times, each for a time of  Standard errors for the histogram bars have a maximum value of  and are invisible on this plot.
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gks925-F2: Loop-size distribution for M = 5 pairs of non-disassociating loop-extruding machines on a lattice of size L = 50. The probability distribution broadens as the bias () increases. Main figure shows results for 1.05 (dot-dashed line), 1.5 (dashed line) and 4.0 (solid line). Inset: comparison of steady-state loop-size distributions for exact statistical theory (solid black line) and kinetic simulation (gray bars); difference between them is negligibly small. The simulation was run times, each for a time of Standard errors for the histogram bars have a maximum value of and are invisible on this plot.

Mentions: Results for the loop-size distribution are shown in Figure 2; for each value of an exponential-like distribution is obtained, corresponding to random fluctuations of loop size in the effective potential.Figure 2.


Self-organization of domain structures by DNA-loop-extruding enzymes.

Alipour E, Marko JF - Nucleic Acids Res. (2012)

Loop-size distribution for M = 5 pairs of non-disassociating loop-extruding machines on a lattice of size L = 50. The probability distribution broadens as the bias () increases. Main figure shows results for  1.05 (dot-dashed line), 1.5 (dashed line) and 4.0 (solid line). Inset: comparison of steady-state loop-size distributions for exact statistical theory (solid black line) and kinetic simulation  (gray bars); difference between them is negligibly small. The simulation was run  times, each for a time of  Standard errors for the histogram bars have a maximum value of  and are invisible on this plot.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3526278&req=5

gks925-F2: Loop-size distribution for M = 5 pairs of non-disassociating loop-extruding machines on a lattice of size L = 50. The probability distribution broadens as the bias () increases. Main figure shows results for 1.05 (dot-dashed line), 1.5 (dashed line) and 4.0 (solid line). Inset: comparison of steady-state loop-size distributions for exact statistical theory (solid black line) and kinetic simulation (gray bars); difference between them is negligibly small. The simulation was run times, each for a time of Standard errors for the histogram bars have a maximum value of and are invisible on this plot.
Mentions: Results for the loop-size distribution are shown in Figure 2; for each value of an exponential-like distribution is obtained, corresponding to random fluctuations of loop size in the effective potential.Figure 2.

Bottom Line: If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained.The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines.This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

View Article: PubMed Central - PubMed

Affiliation: Center for Cell Analysis and Modeling, University of Connecticut Health Sciences Center, Farmington, CT 06030, USA. elnaz.alipour@gmail.com

ABSTRACT
The long chromosomal DNAs of cells are organized into loop domains much larger in size than individual DNA-binding enzymes, presenting the question of how formation of such structures is controlled. We present a model for generation of defined chromosomal loops, based on molecular machines consisting of two coupled and oppositely directed motile elements which extrude loops from the double helix along which they translocate, while excluding one another sterically. If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained. However, if dissociation and rebinding of the machines occurs at a finite rate (finite processivity), the steady state qualitatively changes to a highly ordered 'stacked' configuration with suppressed fluctuations, organizing a single large, stable loop domain anchored by several machines. The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines. Possible realizations of these types of molecular machines are discussed, with a major focus on structural maintenance of chromosome complexes and also with discussion of type I restriction enzymes. This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.

Show MeSH
Related in: MedlinePlus