Limits...
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.

Show MeSH

Related in: MedlinePlus

Condensation of multiple loop domains. (a) Initially condensins (black dumbbell shapes) bind along a long stretch of chromatin (green), between condensation boundary elements (red octagons). (b) As condensation proceeds, condensins organize into a ‘stacked’ configuration at the bases of chromatin loops defined by the boundary elements. The resultant crowding of chromatin at the bases of the loops generates inter-chromatid tension that will drive topo II to remove inter-chromatid entanglements.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gks925-F6: Condensation of multiple loop domains. (a) Initially condensins (black dumbbell shapes) bind along a long stretch of chromatin (green), between condensation boundary elements (red octagons). (b) As condensation proceeds, condensins organize into a ‘stacked’ configuration at the bases of chromatin loops defined by the boundary elements. The resultant crowding of chromatin at the bases of the loops generates inter-chromatid tension that will drive topo II to remove inter-chromatid entanglements.

Mentions: Here, we have considered formation of a single loop domain. The boundaries of our 1D lattice model act as boundary elements for the loop self-organization process. One may ask how the formation of many loop domains along a whole chromosome might be regulated. A straightforward scheme to do this could be based on periodic sequence-defined boundary markers (e.g. proteins bound to specific locations) that would provide a stop signal to the loop-forming machines (by promoting either halting or dissociation). The outcome would be formation of a series of loop domains anchored by discrete clusters of condensing machines, with domain sizes programmed by domain boundaries (Figure 6) (13).Figure 6.


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

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

Condensation of multiple loop domains. (a) Initially condensins (black dumbbell shapes) bind along a long stretch of chromatin (green), between condensation boundary elements (red octagons). (b) As condensation proceeds, condensins organize into a ‘stacked’ configuration at the bases of chromatin loops defined by the boundary elements. The resultant crowding of chromatin at the bases of the loops generates inter-chromatid tension that will drive topo II to remove inter-chromatid entanglements.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gks925-F6: Condensation of multiple loop domains. (a) Initially condensins (black dumbbell shapes) bind along a long stretch of chromatin (green), between condensation boundary elements (red octagons). (b) As condensation proceeds, condensins organize into a ‘stacked’ configuration at the bases of chromatin loops defined by the boundary elements. The resultant crowding of chromatin at the bases of the loops generates inter-chromatid tension that will drive topo II to remove inter-chromatid entanglements.
Mentions: Here, we have considered formation of a single loop domain. The boundaries of our 1D lattice model act as boundary elements for the loop self-organization process. One may ask how the formation of many loop domains along a whole chromosome might be regulated. A straightforward scheme to do this could be based on periodic sequence-defined boundary markers (e.g. proteins bound to specific locations) that would provide a stop signal to the loop-forming machines (by promoting either halting or dissociation). The outcome would be formation of a series of loop domains anchored by discrete clusters of condensing machines, with domain sizes programmed by domain boundaries (Figure 6) (13).Figure 6.

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