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Hierarchies in eukaryotic genome organization: Insights from polymer theory and simulations.

Iyer BV, Kenward M, Arya G - BMC Biophys (2011)

Bottom Line: Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus.Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function.Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of NanoEngineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA. garya@ucsd.edu.

ABSTRACT
Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus. Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function. Elegant microscopy and chromosome conformation capture techniques supported by analysis based on polymer models are important steps in this direction. Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.

No MeSH data available.


Nucleosome Depletion. Schematic of nucleosomal depletion associated persistence length modification and consequent local conformation change in the cell nucleus.  and  refer to the initial and final persistence length, respectively.
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Figure 4: Nucleosome Depletion. Schematic of nucleosomal depletion associated persistence length modification and consequent local conformation change in the cell nucleus. and refer to the initial and final persistence length, respectively.

Mentions: As discussed earlier, chromatin exists in a highly dynamic state within the cell nucleus. In fact, histone octamers are constantly being dissolved and rebound with the average genome-wide nucleosome occupancies being less than 75% [32]. Heermann and coworkers [78,79] have recently examined the effects of such depletion events on the persistence length and conformation of nucleosome arrays (Figure 4). They employed an extended two-angle (E2A) model [25,32], which allows examination of very long nucleosome arrays containing >1000 nucleosomes. An adaptation of the E2A model with experimental distribution of nucleosome repeat lengths yields a quantitative estimate for persistence length modification. Recent Monte Carlo (MC) simulations based on this adaptation indicate a decrease of Lp from an initial value of 280 nm to 140 nm with ≈ 20% increase in the nucleosome skip probability [78]. This leads to sharp bends in the fiber allowing for formation of loops in the kilo base pair range [79], an important feature of genome organization visualized in experiments [69].


Hierarchies in eukaryotic genome organization: Insights from polymer theory and simulations.

Iyer BV, Kenward M, Arya G - BMC Biophys (2011)

Nucleosome Depletion. Schematic of nucleosomal depletion associated persistence length modification and consequent local conformation change in the cell nucleus.  and  refer to the initial and final persistence length, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102647&req=5

Figure 4: Nucleosome Depletion. Schematic of nucleosomal depletion associated persistence length modification and consequent local conformation change in the cell nucleus. and refer to the initial and final persistence length, respectively.
Mentions: As discussed earlier, chromatin exists in a highly dynamic state within the cell nucleus. In fact, histone octamers are constantly being dissolved and rebound with the average genome-wide nucleosome occupancies being less than 75% [32]. Heermann and coworkers [78,79] have recently examined the effects of such depletion events on the persistence length and conformation of nucleosome arrays (Figure 4). They employed an extended two-angle (E2A) model [25,32], which allows examination of very long nucleosome arrays containing >1000 nucleosomes. An adaptation of the E2A model with experimental distribution of nucleosome repeat lengths yields a quantitative estimate for persistence length modification. Recent Monte Carlo (MC) simulations based on this adaptation indicate a decrease of Lp from an initial value of 280 nm to 140 nm with ≈ 20% increase in the nucleosome skip probability [78]. This leads to sharp bends in the fiber allowing for formation of loops in the kilo base pair range [79], an important feature of genome organization visualized in experiments [69].

Bottom Line: Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus.Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function.Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of NanoEngineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0448, USA. garya@ucsd.edu.

ABSTRACT
Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus. Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function. Elegant microscopy and chromosome conformation capture techniques supported by analysis based on polymer models are important steps in this direction. Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.

No MeSH data available.