Distinct polymer physics principles govern chromatin dynamics in mouse and Drosophila topological domains.
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.
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.
Vuthy
V
Ea
Institut de Génétique Humaine, UPR 1142, CNRS, Montpellier, France. sexton@igbmc.fr.
Tom
T
Sexton
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. thierry.gostan@igmm.cnrs.fr.
Thierry
T
Gostan
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. laurie.herviou@voila.fr.
Laurie
L
Herviou
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. marie-odile.baudement@igmm.cnrs.fr.
Marie-Odile
MO
Baudement
School of Biology and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA. yunzhe_zhang@hotmail.com.
Yunzhe
Y
Zhang
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. soizik.berlivet@igmm.cnrs.fr.
Soizik
S
Berlivet
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. Marie-Noelle.Taha@univ-montp2.fr.
Marie-Noëlle
MN
Le Lay-Taha
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. guy.cathala@igmm.cnrs.fr.|CNRS GDR 3536 UPMC, Sorbonne universités, Paris, France. guy.cathala@igmm.cnrs.fr.
Guy
G
Cathala
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. lesne@lptmc.jussieu.fr.|CNRS GDR 3536 UPMC, Sorbonne universités, Paris, France. lesne@lptmc.jussieu.fr.|Laboratoire de Physique de la Matière Condensée, CNRS UMR 7600, UPMC, Sorbonne universités, Paris, France. lesne@lptmc.jussieu.fr.
Annick
A
Lesne
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. victor@lptmc.jussieu.fr.|CNRS GDR 3536 UPMC, Sorbonne universités, Paris, France. victor@lptmc.jussieu.fr.|Laboratoire de Physique de la Matière Condensée, CNRS UMR 7600, UPMC, Sorbonne universités, Paris, France. victor@lptmc.jussieu.fr.
Jean-Marc
JM
Victor
School of Biology and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA. yuhong.fan@biology.gatech.edu.
Yuhong
Y
Fan
Institut de Génétique Humaine, UPR 1142, CNRS, Montpellier, France. Giacomo.Cavalli@igh.cnrs.fr.|CNRS GDR 3536 UPMC, Sorbonne universités, Paris, France. Giacomo.Cavalli@igh.cnrs.fr.
Giacomo
G
Cavalli
Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université de Montpellier, 1919 Route de Mende, 34293, Montpellier, Cedex 5, France. forne@igmm.cnrs.fr.|CNRS GDR 3536 UPMC, Sorbonne universités, Paris, France. forne@igmm.cnrs.fr.
Thierry
T
Forné
D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry*; D004331:Drosophila melanogaster / Q000235:genetics*; D044127:Epigenesis, Genetic; D008099:Liver / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015233:Models, Statistical; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology; D009690:Nucleic Acid Conformation
D002843:Chromatin; D004247:DNA