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Distinct polymer physics principles govern chromatin dynamics in mouse and Drosophila topological domains.

Ea V, Sexton T, Gostan T, Herviou L, Baudement MO, Zhang Y, Berlivet S, Le Lay-Taha MN, Cathala G, Lesne A, Victor JM, Fan Y, Cavalli G, Forné T - BMC Genomics (2015)

Bottom Line: Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus-specific interaction takes place.Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells.Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. vuthy.ea@igmm.cnrs.fr.

ABSTRACT

Background: In higher eukaryotes, the genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts. While a crumpled/fractal globule organization has received experimental supports at higher-order levels, the organization principles that govern chromatin dynamics within these TADs remain unclear. Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus-specific interaction takes place.

Results: Here, we use data from diverse 3C-derived methods to explore chromatin dynamics within mouse and Drosophila TADs. In mouse Embryonic Stem Cells (mESC), that possess large TADs (median size of 840 kb), we show that the statistical helix model, but not globule models, is relevant not only in gene-rich TADs, but also in gene-poor and gene-desert TADs. Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells. Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization. In Drosophila, which possesses TADs of smaller sizes (median size of 70 kb), we show that, while chromatin compaction and flexibility are finely tuned according to the epigenetic landscape, chromatin dynamics within TADs is generally compatible with an unconstrained polymer configuration.

Conclusions: Models issued from polymer physics can accurately describe the organization principles governing chromatin dynamics in both mouse and Drosophila TADs. However, constraints applied on this dynamics within mammalian TADs have a peculiar impact resulting in a statistical helix organization.

No MeSH data available.


Related in: MedlinePlus

Fitting globule models to contact frequencies quantified in mESC. Experimental 3C-qPCR data obtained for wt mESC in gene-rich TADs (Fig. 2) have been displayed into a Log-Log plot and globule models were fitted to the following power-law: X(s) = k*sα (adapted from Eq. 6 and Eq. 9 from ref. [20]), where X(s) is the cross-linking frequency, s (in kb) is the site separation along the genome, K is representing the efficiency of cross-linking and the exponent α is the slope associated to this power-law. Best-fits (using the nls object of the R software) show that the slope associated to our experimental data (red line) is approximately α = −1/2 (−0.52) with a correlation coefficient R2 = 0.47, while correlation coefficients associated to the equilibrium (α = −3/2) (black line) or crumpled globules (α = −1) (green line) are much lower
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Fig1: Fitting globule models to contact frequencies quantified in mESC. Experimental 3C-qPCR data obtained for wt mESC in gene-rich TADs (Fig. 2) have been displayed into a Log-Log plot and globule models were fitted to the following power-law: X(s) = k*sα (adapted from Eq. 6 and Eq. 9 from ref. [20]), where X(s) is the cross-linking frequency, s (in kb) is the site separation along the genome, K is representing the efficiency of cross-linking and the exponent α is the slope associated to this power-law. Best-fits (using the nls object of the R software) show that the slope associated to our experimental data (red line) is approximately α = −1/2 (−0.52) with a correlation coefficient R2 = 0.47, while correlation coefficients associated to the equilibrium (α = −3/2) (black line) or crumpled globules (α = −1) (green line) are much lower

Mentions: To assess whether such organization principles apply to chromatin dynamics within TADs, we thus performed quantitative 3C experiments in the different TADs described above and, using Log-Log plots, we showed that gene-rich, as well as gene-poor and gene-desert TADs display slopes superior to −1 (−0.60 to −0.48) (Fig. 1) which are incompatible with the equilibrium or crumpled globule models. Therefore, neither the equilibrium nor the crumpled globule models accurately reproduce chromatin dynamics within mammalian TADs.Fig. 1


Distinct polymer physics principles govern chromatin dynamics in mouse and Drosophila topological domains.

Ea V, Sexton T, Gostan T, Herviou L, Baudement MO, Zhang Y, Berlivet S, Le Lay-Taha MN, Cathala G, Lesne A, Victor JM, Fan Y, Cavalli G, Forné T - BMC Genomics (2015)

Fitting globule models to contact frequencies quantified in mESC. Experimental 3C-qPCR data obtained for wt mESC in gene-rich TADs (Fig. 2) have been displayed into a Log-Log plot and globule models were fitted to the following power-law: X(s) = k*sα (adapted from Eq. 6 and Eq. 9 from ref. [20]), where X(s) is the cross-linking frequency, s (in kb) is the site separation along the genome, K is representing the efficiency of cross-linking and the exponent α is the slope associated to this power-law. Best-fits (using the nls object of the R software) show that the slope associated to our experimental data (red line) is approximately α = −1/2 (−0.52) with a correlation coefficient R2 = 0.47, while correlation coefficients associated to the equilibrium (α = −3/2) (black line) or crumpled globules (α = −1) (green line) are much lower
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536789&req=5

Fig1: Fitting globule models to contact frequencies quantified in mESC. Experimental 3C-qPCR data obtained for wt mESC in gene-rich TADs (Fig. 2) have been displayed into a Log-Log plot and globule models were fitted to the following power-law: X(s) = k*sα (adapted from Eq. 6 and Eq. 9 from ref. [20]), where X(s) is the cross-linking frequency, s (in kb) is the site separation along the genome, K is representing the efficiency of cross-linking and the exponent α is the slope associated to this power-law. Best-fits (using the nls object of the R software) show that the slope associated to our experimental data (red line) is approximately α = −1/2 (−0.52) with a correlation coefficient R2 = 0.47, while correlation coefficients associated to the equilibrium (α = −3/2) (black line) or crumpled globules (α = −1) (green line) are much lower
Mentions: To assess whether such organization principles apply to chromatin dynamics within TADs, we thus performed quantitative 3C experiments in the different TADs described above and, using Log-Log plots, we showed that gene-rich, as well as gene-poor and gene-desert TADs display slopes superior to −1 (−0.60 to −0.48) (Fig. 1) which are incompatible with the equilibrium or crumpled globule models. Therefore, neither the equilibrium nor the crumpled globule models accurately reproduce chromatin dynamics within mammalian TADs.Fig. 1

Bottom Line: Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus-specific interaction takes place.Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells.Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. vuthy.ea@igmm.cnrs.fr.

ABSTRACT

Background: In higher eukaryotes, the genome is partitioned into large "Topologically Associating Domains" (TADs) in which the chromatin displays favoured long-range contacts. While a crumpled/fractal globule organization has received experimental supports at higher-order levels, the organization principles that govern chromatin dynamics within these TADs remain unclear. Using simple polymer models, we previously showed that, in mouse liver cells, gene-rich domains tend to adopt a statistical helix shape when no significant locus-specific interaction takes place.

Results: Here, we use data from diverse 3C-derived methods to explore chromatin dynamics within mouse and Drosophila TADs. In mouse Embryonic Stem Cells (mESC), that possess large TADs (median size of 840 kb), we show that the statistical helix model, but not globule models, is relevant not only in gene-rich TADs, but also in gene-poor and gene-desert TADs. Interestingly, this statistical helix organization is considerably relaxed in mESC compared to liver cells, indicating that the impact of the constraints responsible for this organization is weaker in pluripotent cells. Finally, depletion of histone H1 in mESC alters local chromatin flexibility but not the statistical helix organization. In Drosophila, which possesses TADs of smaller sizes (median size of 70 kb), we show that, while chromatin compaction and flexibility are finely tuned according to the epigenetic landscape, chromatin dynamics within TADs is generally compatible with an unconstrained polymer configuration.

Conclusions: Models issued from polymer physics can accurately describe the organization principles governing chromatin dynamics in both mouse and Drosophila TADs. However, constraints applied on this dynamics within mammalian TADs have a peculiar impact resulting in a statistical helix organization.

No MeSH data available.


Related in: MedlinePlus